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Dr. Ogun Adebali
Sabanci University

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0 DNA Repair
0 Computational biology
0 phylogenetic analyses
0 molecular evolution and genomics
0 Genomics and personilized medicine

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Journal article
Published: 06 August 2021 in BMC Genomics
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Nucleotide excision repair is the primary DNA repair mechanism that removes bulky DNA adducts such as UV-induced pyrimidine dimers. Correspondingly, genome-wide mapping of nucleotide excision repair with eXcision Repair sequencing (XR-seq), provides comprehensive profiling of DNA damage repair. A number of XR-seq experiments at a variety of conditions for different damage types revealed heterogenous repair in the human genome. Although human repair profiles were extensively studied, how repair maps vary between primates is yet to be investigated. Here, we characterized the genome-wide UV-induced damage repair in gray mouse lemur, Microcebus murinus, in comparison to human. We derived fibroblast cell lines from mouse lemur, exposed them to UV irradiation, and analyzed the repair events genome-wide using the XR-seq protocol. Mouse lemur repair profiles were analyzed in comparison to the equivalent human fibroblast datasets. We found that overall UV sensitivity, repair efficiency, and transcription-coupled repair levels differ between the two primates. Despite this, comparative analysis of human and mouse lemur fibroblasts revealed that genome-wide repair profiles of the homologous regions are highly correlated, and this correlation is stronger for highly expressed genes. With the inclusion of an additional XR-seq sample derived from another human cell line in the analysis, we found that fibroblasts of the two primates repair UV-induced DNA lesions in a more similar pattern than two distinct human cell lines do. Our results suggest that mouse lemurs and humans, and possibly primates in general, share a homologous repair mechanism as well as genomic variance distribution, albeit with their variable repair efficiency. This result also emphasizes the deep homologies of individual tissue types across the eukaryotic phylogeny. The online version contains supplementary material available at 10.1186/s12864-021-07898-3.

ACS Style

Umit Akkose; Veysel Ogulcan Kaya; Laura Lindsey-Boltz; Zeynep Karagoz; Adam D. Brown; Peter A. Larsen; Anne D. Yoder; Aziz Sancar; Ogun Adebali. Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events. BMC Genomics 2021, 22, 1 .

AMA Style

Umit Akkose, Veysel Ogulcan Kaya, Laura Lindsey-Boltz, Zeynep Karagoz, Adam D. Brown, Peter A. Larsen, Anne D. Yoder, Aziz Sancar, Ogun Adebali. Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events. BMC Genomics. 2021; 22 ():1.

Chicago/Turabian Style

Umit Akkose; Veysel Ogulcan Kaya; Laura Lindsey-Boltz; Zeynep Karagoz; Adam D. Brown; Peter A. Larsen; Anne D. Yoder; Aziz Sancar; Ogun Adebali. 2021. "Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events." BMC Genomics 22, no. : 1.

Journal article
Published: 02 March 2021 in Viruses
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Understanding SARS-CoV-2 evolution is a fundamental effort in coping with the COVID-19 pandemic. The virus genomes have been broadly evolving due to the high number of infected hosts world-wide. Mutagenesis and selection are two inter-dependent mechanisms of virus diversification. However, which mechanisms contribute to the mutation profiles of SARS-CoV-2 remain under-explored. Here, we delineate the contribution of mutagenesis and selection to the genome diversity of SARS-CoV-2 isolates. We generated a comprehensive phylogenetic tree with representative genomes. Instead of counting mutations relative to the reference genome, we identified each mutation event at the nodes of the phylogenetic tree. With this approach, we obtained the mutation events that are independent of each other and generated the mutation profile of SARS-CoV-2 genomes. The results suggest that the heterogeneous mutation patterns are mainly reflections of host (i) antiviral mechanisms that are achieved through APOBEC, ADAR, and ZAP proteins, and (ii) probable adaptation against reactive oxygen species.

ACS Style

Cem Azgari; Zeynep Kilinc; Berk Turhan; Defne Circi; Ogun Adebali. The Mutation Profile of SARS-CoV-2 Is Primarily Shaped by the Host Antiviral Defense. Viruses 2021, 13, 394 .

AMA Style

Cem Azgari, Zeynep Kilinc, Berk Turhan, Defne Circi, Ogun Adebali. The Mutation Profile of SARS-CoV-2 Is Primarily Shaped by the Host Antiviral Defense. Viruses. 2021; 13 (3):394.

Chicago/Turabian Style

Cem Azgari; Zeynep Kilinc; Berk Turhan; Defne Circi; Ogun Adebali. 2021. "The Mutation Profile of SARS-CoV-2 Is Primarily Shaped by the Host Antiviral Defense." Viruses 13, no. 3: 394.

Preprint content
Published: 04 February 2021
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Understanding SARS-CoV-2 evolution is a fundamental effort in coping with the COVID-19 pandemic. The virus genomes have been broadly evolving due to the high number of infected hosts world-wide. Mutagenesis and selection are the two inter-dependent mechanisms of virus diversification. However, which mechanisms contribute to the mutation profiles of SARS-CoV-2 remain under-explored. Here, we delineate the contribution of mutagenesis and selection to the genome diversity of SARS-CoV-2 isolates. We generated a comprehensive phylogenetic tree with representative genomes. Instead of counting mutations relative to the reference genome, we identified each mutation event at the nodes of the phylogenetic tree. With this approach, we obtained the mutation events that are independent of each other and generated the mutation profile of SARS-CoV-2 genomes. The results suggest that the heterogeneous mutation patterns are mainly reflections of host (i) antiviral mechanisms that are achieved through APOBEC, ADAR, and ZAP proteins and (ii) probable adaptation against reactive oxygen species. Importance SARS-CoV-2 genomes are evolving worldwide. Revealing the evolutionary characteristics of SARS-CoV-2 is essential to understand host-virus interactions. Here, we aim to understand whether mutagenesis or selection is the primary driver of SARS-CoV-2 evolution. This study provides an unbiased computational method for profiling and analyzing independently occurring SARS-CoV-2 mutations. The results point out three host antiviral mechanisms shaping the mutational profile of SARS-CoV-2 through APOBEC, ADAR, and ZAP proteins. Besides, reactive oxygen species might have an impact on the SARS-CoV-2 mutagenesis.

ACS Style

Cem Azgari; Zeynep Kilinc; Berk Turhan; Defne Circi; Ogun Adebali. The mutation profile of SARS-CoV-2 is primarily shaped by the host antiviral defense. 2021, 1 .

AMA Style

Cem Azgari, Zeynep Kilinc, Berk Turhan, Defne Circi, Ogun Adebali. The mutation profile of SARS-CoV-2 is primarily shaped by the host antiviral defense. . 2021; ():1.

Chicago/Turabian Style

Cem Azgari; Zeynep Kilinc; Berk Turhan; Defne Circi; Ogun Adebali. 2021. "The mutation profile of SARS-CoV-2 is primarily shaped by the host antiviral defense." , no. : 1.

Preprint content
Published: 08 November 2020
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Long non-coding RNAs (lncRNAs) are the largest class of non-coding RNAs (ncRNAs). However, recent experimental evidence has shown that some lncRNAs contain small open reading frames (sORFs) that are translated into functional micropeptides. Current methods to detect misannotated lncRNAs rely on ribosome-profiling (ribo-seq) experiments, which are expensive and cell-type dependent. In addition, while very accurate machine learning models have been trained to distinguish between coding and non-coding sequences, little attention has been paid to the increasing evidence about the incorrect ground-truth labels of some lncRNAs in the underlying training datasets. We present a framework that leverages deep learning models’ training dynamics to determine whether a given lncRNA transcript is misannotated. Our models achieve AUC scores > 91% and AUPR > 93% in classifying non-coding vs. coding sequences while allowing us to identify possible misannotated lncRNAs present in the dataset. Our results overlap significantly with a set of experimentally validated misannotated lncRNAs as well as with coding sORFs within lncRNAs found by a ribo-seq dataset. The general framework applied here offers promising potential for use in curating datasets used for training coding potential predictors and assisting experimental efforts in characterizing the hidden proteome encoded by misannotated lncRNAs. Source code is available athttps://github.com/nabiafshan/DetectingMisannotatedLncRNAs.

ACS Style

Afshan Nabi; Ogun Adebali; Oznur Tastan. Detecting Misannotated Long Non-coding RNAs with Training Dynamics of Deep Sequence Classification. 2020, 1 .

AMA Style

Afshan Nabi, Ogun Adebali, Oznur Tastan. Detecting Misannotated Long Non-coding RNAs with Training Dynamics of Deep Sequence Classification. . 2020; ():1.

Chicago/Turabian Style

Afshan Nabi; Ogun Adebali; Oznur Tastan. 2020. "Detecting Misannotated Long Non-coding RNAs with Training Dynamics of Deep Sequence Classification." , no. : 1.

Journal article
Published: 21 June 2020 in TURKISH JOURNAL OF BIOLOGY
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COVID-19 has effectively spread worldwide. As of May 2020, Turkey is among the top ten countries with the most cases. A comprehensive genomic characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a phylogenetic tree with globally obtained 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in comparison with the previously annotated classifications. We performed a phylogenetic analysis of the first 30 SARS-CoV-2 genomes isolated and sequenced in Turkey. We suggest that the first introduction of the virus to the country is earlier than the first reported case of infection. Virus genomes isolated from Turkey are dispersed among most types in the phylogenetic tree. We find 2 of the seventeen subclusters enriched with the isolates of Turkey, which likely have spread expansively in the country. Finally, we traced virus genomes based on their phylogenetic placements. This analysis suggested multiple independent international introductions of the virus and revealed a hub for the inland transmission. We released a web application to track the global and interprovincial virus spread of the isolates from Turkey in comparison to thousands of genomes worldwide.

ACS Style

Ogün Adebali; Aylin Bircan; Defne Çirci; Burak Işlek; Zeynep Kilinç; Berkay Selçuk; Berk Turhan. Phylogenetic analysis of SARS-CoV-2 genomes in Turkey. TURKISH JOURNAL OF BIOLOGY 2020, 44, 146 -156.

AMA Style

Ogün Adebali, Aylin Bircan, Defne Çirci, Burak Işlek, Zeynep Kilinç, Berkay Selçuk, Berk Turhan. Phylogenetic analysis of SARS-CoV-2 genomes in Turkey. TURKISH JOURNAL OF BIOLOGY. 2020; 44 (3):146-156.

Chicago/Turabian Style

Ogün Adebali; Aylin Bircan; Defne Çirci; Burak Işlek; Zeynep Kilinç; Berkay Selçuk; Berk Turhan. 2020. "Phylogenetic analysis of SARS-CoV-2 genomes in Turkey." TURKISH JOURNAL OF BIOLOGY 44, no. 3: 146-156.

Preprint content
Published: 15 May 2020
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COVID-19 has effectively spread worldwide. As of May 2020, Turkey is among the top ten countries with the most cases. A comprehensive genomic characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a phylogenetic tree with globally obtained 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in comparison with the previously annotated classifications. We performed a phylogenetic analysis of the first thirty SARS-CoV-2 genomes isolated and sequenced in Turkey. We suggest that the first introduction of the virus to the country is earlier than the first reported case of infection. Virus genomes isolated from Turkey are dispersed among most types in the phylogenetic tree. We find two of the seventeen sub-clusters enriched with the isolates of Turkey, which likely have spread expansively in the country. Finally, we traced virus genomes based on their phylogenetic placements. This analysis suggested multiple independent international introductions of the virus and revealed a hub for the inland transmission. We released a web application to track the global and interprovincial virus spread of the isolates from Turkey in comparison to thousands of genomes worldwide.

ACS Style

Ogün Adebalı; Aylin Bırcan; Defne Çırcı; Burak Işlek; Zeynep Kilinç; Berkay Selçuk; Berk Turhan. Phylogenetic Analysis of SARS-CoV-2 Genomes in Turkey. 2020, 1 .

AMA Style

Ogün Adebalı, Aylin Bırcan, Defne Çırcı, Burak Işlek, Zeynep Kilinç, Berkay Selçuk, Berk Turhan. Phylogenetic Analysis of SARS-CoV-2 Genomes in Turkey. . 2020; ():1.

Chicago/Turabian Style

Ogün Adebalı; Aylin Bırcan; Defne Çırcı; Burak Işlek; Zeynep Kilinç; Berkay Selçuk; Berk Turhan. 2020. "Phylogenetic Analysis of SARS-CoV-2 Genomes in Turkey." , no. : 1.

Preprint content
Published: 06 April 2020
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Nucleotide excision repair is the primary DNA repair mechanism that removes bulky DNA adducts such as UV-induced pyrimidine dimers. Correspondingly, genome-wide mapping of nucleotide excision repair with eXcision Repair sequencing (XR-seq), provides comprehensive profiling of DNA damage repair. A number of XR-seq experiments at a variety of conditions for different damage types revealed heterogenous repair in the human genome. Although human repair profiles were extensively studied, how repair maps vary between primates is yet to be investigated. Here, we characterized the genome-wide UV-induced damage repair in gray mouse lemur, Microcebus murinus, in comparison to human. Mouse lemurs are strictly nocturnal, are the world’s smallest living primates, and last shared a common ancestor with humans at least 60 million years ago. We derived fibroblast cell lines from mouse lemur, exposed them to UV irradiation. The following repair events were captured genome-wide through the XR-seq protocol. Mouse lemur repair profiles were analyzed in comparison to the equivalent human fibroblast datasets. We found that overall UV sensitivity, repair efficiency, and transcription-coupled repair levels differ between the two primates. Despite this, comparative analysis of human and mouse lemur fibroblasts revealed that genome-wide repair profiles of the homologous regions are highly correlated. This correlation is stronger for the highly expressed genes. With the inclusion of an additional XR-seq sample derived from another human cell line in the analysis, we found that fibroblasts of the two primates repair UV-induced DNA lesions in a more similar pattern than two distinct human cell lines do. Our results suggest that mouse lemurs and humans, and possibly primates in general, share a homologous repair mechanism as well as genomic variance distribution, albeit with their variable repair efficiency. This result also emphasizes the deep homologies of individual tissue types across the eukaryotic phylogeny.

ACS Style

Umit Akkose; Veysel Ogulcan Kaya; Laura Lindsey-Boltz; Zeynep Karagoz; Adam D. Brown; Peter A. Larsen; Anne D. Yoder; Aziz Sancar; Ogun Adebali. Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events. 2020, 1 .

AMA Style

Umit Akkose, Veysel Ogulcan Kaya, Laura Lindsey-Boltz, Zeynep Karagoz, Adam D. Brown, Peter A. Larsen, Anne D. Yoder, Aziz Sancar, Ogun Adebali. Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events. . 2020; ():1.

Chicago/Turabian Style

Umit Akkose; Veysel Ogulcan Kaya; Laura Lindsey-Boltz; Zeynep Karagoz; Adam D. Brown; Peter A. Larsen; Anne D. Yoder; Aziz Sancar; Ogun Adebali. 2020. "Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events." , no. : 1.

Journal article
Published: 01 January 2020 in Turkish Journal of Immunology
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ACS Style

Sofia Piepoli; Bahar Shamloo; Aylin Bircan; Ogun Adebali; Batu Erman. Molecular Biology of SARS-CoV-2. Turkish Journal of Immunology 2020, 8, 73 -88.

AMA Style

Sofia Piepoli, Bahar Shamloo, Aylin Bircan, Ogun Adebali, Batu Erman. Molecular Biology of SARS-CoV-2. Turkish Journal of Immunology. 2020; 8 (2):73-88.

Chicago/Turabian Style

Sofia Piepoli; Bahar Shamloo; Aylin Bircan; Ogun Adebali; Batu Erman. 2020. "Molecular Biology of SARS-CoV-2." Turkish Journal of Immunology 8, no. 2: 73-88.

Journal article
Published: 22 November 2019 in Nucleic Acids Research
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Bacteria and archaea employ dedicated signal transduction systems that modulate gene expression, second-messenger turnover, quorum sensing, biofilm formation, motility, host-pathogen and beneficial interactions. The updated MiST database provides a comprehensive classification of microbial signal transduction systems. This update is a result of a substantial scaling to accommodate constantly growing microbial genomic data. More than 125 000 genomes, 516 million genes and almost 100 million unique protein sequences are currently stored in the database. For each bacterial and archaeal genome, MiST 3.0 provides a complete signal transduction profile, thus facilitating theoretical and experimental studies on signal transduction and gene regulation. New software infrastructure and distributed pipeline implemented in MiST 3.0 enable regular genome updates based on the NCBI RefSeq database. A novel MiST feature is the integration of unique profile HMMs to link complex chemosensory systems with corresponding chemoreceptors in bacterial and archaeal genomes. The data can be explored online or via RESTful API (freely available at https://mistdb.com).

ACS Style

Vadim Gumerov; Davi R Ortega; Ogun Adebali; Luke E Ulrich; Igor B Zhulin. MiST 3.0: an updated microbial signal transduction database with an emphasis on chemosensory systems. Nucleic Acids Research 2019, 48, D459 -D464.

AMA Style

Vadim Gumerov, Davi R Ortega, Ogun Adebali, Luke E Ulrich, Igor B Zhulin. MiST 3.0: an updated microbial signal transduction database with an emphasis on chemosensory systems. Nucleic Acids Research. 2019; 48 (D1):D459-D464.

Chicago/Turabian Style

Vadim Gumerov; Davi R Ortega; Ogun Adebali; Luke E Ulrich; Igor B Zhulin. 2019. "MiST 3.0: an updated microbial signal transduction database with an emphasis on chemosensory systems." Nucleic Acids Research 48, no. D1: D459-D464.

Journal article
Published: 01 April 2019 in Journal of Biological Chemistry
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Embryonic stem cells can self-renew and differentiate, holding great promise for regenerative medicine. They also employ multiple mechanisms to preserve the integrity of their genomes. Nucleotide excision repair, a versatile repair mechanism, removes bulky DNA adducts from the genome. However, the dynamics of the capacity of nucleotide excision repair during stem cell differentiation remain unclear. Here, using immunoslot blot assay, we measured repair rates of UV-induced DNA damage during differentiation of human embryonic carcinoma (NTERA-2) cells into neurons and muscle cells. Our results revealed that the capacity of nucleotide excision repair increases as cell differentiation progresses. We also found that inhibition of the apoptotic signaling pathway has no effect on nucleotide excision repair capacity. Furthermore, RNA-Seq–based transcriptomic analysis indicated that expression levels of four core repair factors, xeroderma pigmentosum (XP) complementation group A (XPA), XPC, XPG, and XPF-ERCC1, are progressively up-regulated during differentiation, but not those of replication protein A (RPA) and transcription factor IIH (TFIIH). Together, our findings reveal that increase of nucleotide excision repair capacity accompanies cell differentiation, supported by the up-regulated transcription of genes encoding DNA repair enzymes during differentiation of two distinct cell lineages.

ACS Style

Wentao Li; Wenjie Liu; Ayano Kakoki; Rujin Wang; Ogun Adebali; Yuchao Jiang; Aziz Sancar. Nucleotide excision repair capacity increases during differentiation of human embryonic carcinoma cells into neurons and muscle cells. Journal of Biological Chemistry 2019, 294, 5914 -5922.

AMA Style

Wentao Li, Wenjie Liu, Ayano Kakoki, Rujin Wang, Ogun Adebali, Yuchao Jiang, Aziz Sancar. Nucleotide excision repair capacity increases during differentiation of human embryonic carcinoma cells into neurons and muscle cells. Journal of Biological Chemistry. 2019; 294 (15):5914-5922.

Chicago/Turabian Style

Wentao Li; Wenjie Liu; Ayano Kakoki; Rujin Wang; Ogun Adebali; Yuchao Jiang; Aziz Sancar. 2019. "Nucleotide excision repair capacity increases during differentiation of human embryonic carcinoma cells into neurons and muscle cells." Journal of Biological Chemistry 294, no. 15: 5914-5922.

Journal article
Published: 18 January 2019 in Nature Communications
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The platinum-based drug cisplatin is a widely used first-line therapy for several cancers. Cisplatin interacts with DNA mainly in the form of Pt-d(GpG) di-adduct, which stalls cell proliferation and activates DNA damage response. Although cisplatin shows a broad spectrum of anticancer activity, its utility is limited due to acquired drug resistance and toxicity to non-targeted tissues. Here, by integrating genome-wide high-throughput Damage-seq, XR-seq, and RNA-seq approaches, along with publicly available epigenomic data, we systematically study the genome-wide profiles of cisplatin damage formation and excision repair in mouse kidney, liver, lung and spleen. We find different DNA damage and repair spectra across mouse organs, which are associated with tissue-specific transcriptomic and epigenomic profiles. The framework and the multi-omics data we present here constitute an unbiased foundation for understanding the mechanisms of cellular response to cisplatin. Our approach should be applicable for studying drug resistance and for tailoring cancer chemotherapy regimens. Cisplatin, a platinum chemotherapeutic agent, is widely used to treat several cancers. Here Yimit et al. revert to genome-wide approaches to map and analyze cisplatin damage formation and excision repair with single nucleotide resolution across different mice organs following platinum treatment.

ACS Style

Askar Yimit; Ogun Adebali; Aziz Sancar; Yuchao Jiang. Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs. Nature Communications 2019, 10, 1 -11.

AMA Style

Askar Yimit, Ogun Adebali, Aziz Sancar, Yuchao Jiang. Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs. Nature Communications. 2019; 10 (1):1-11.

Chicago/Turabian Style

Askar Yimit; Ogun Adebali; Aziz Sancar; Yuchao Jiang. 2019. "Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs." Nature Communications 10, no. 1: 1-11.

Journal article
Published: 14 December 2018 in Nature Protocols
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Nucleotide excision repair is a versatile mechanism to repair a variety of bulky DNA adducts. We developed excision repair sequencing (XR-seq) to study nucleotide excision repair of DNA adducts in humans, mice, Arabidopsis thaliana, yeast and Escherichia coli. In this protocol, the excised oligomers, generated in the nucleotide excision repair reaction, are isolated by cell lysis and fractionation, followed by immunoprecipitation with damage- or repair factor-specific antibodies from the non-chromatin fraction. The single-stranded excised oligomers are ligated to adapters and re-immunoprecipitated with damage-specific antibodies. The DNA damage in the excised oligomers is then reversed by enzymatic or chemical reactions before being converted into a sequencing library by PCR amplification. Alternatively, the excised oligomers containing DNA damage, especially those containing irreversible DNA damage such as benzo[a]pyrene-induced DNA adducts, can be converted to a double-stranded DNA (dsDNA) form by using appropriate translesion DNA synthesis (TLS) polymerases and then can be amplified by PCR. The current genome-wide approaches for studying repair measure the loss of damage signal with time, which limits their resolution. By contrast, an advantage of XR-seq is that the repair signal is directly detected above a background of zero. An XR-seq library using the protocol described here can be obtained in 7-9 d.

ACS Style

Jinchuan Hu; Wentao Li; Ogun Adebali; Yanyan Yang; Onur Oztas; Christopher P. Selby; Aziz Sancar. Genome-wide mapping of nucleotide excision repair with XR-seq. Nature Protocols 2018, 14, 248 -282.

AMA Style

Jinchuan Hu, Wentao Li, Ogun Adebali, Yanyan Yang, Onur Oztas, Christopher P. Selby, Aziz Sancar. Genome-wide mapping of nucleotide excision repair with XR-seq. Nature Protocols. 2018; 14 (1):248-282.

Chicago/Turabian Style

Jinchuan Hu; Wentao Li; Ogun Adebali; Yanyan Yang; Onur Oztas; Christopher P. Selby; Aziz Sancar. 2018. "Genome-wide mapping of nucleotide excision repair with XR-seq." Nature Protocols 14, no. 1: 248-282.

Journal article
Published: 07 May 2018 in Proceedings of the National Academy of Sciences
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Cisplatin is a major cancer chemotherapeutic drug. It kills cancer cells by damaging their DNA, mainly in the form of Pt-d(GpG) diadducts. However, it also has serious side effects, including nephrotoxicity and hepatotoxicity that limit its usefulness. Chronotherapy is taking circadian time into account during therapy to improve the therapeutic index, by improving efficacy and/or limiting toxicity. To this end, we tested the impact of clock time on excision repair of cisplatin-induced DNA damage at single-nucleotide resolution across the genome in mouse kidney and liver. We found that genome repair is controlled by two circadian programs. Repair of the transcribed strand (TS) of active, circadian-controlled genes is dictated by each gene’s phase of transcription, which falls across the circadian cycle with prominent peaks at dawn and dusk. In contrast, repair of the nontranscribed strand (NTS) of all genes, repair of intergenic DNA, and global repair overall peaks at Zeitgeber time ZT08, as basal repair capacity, which is controlled by the circadian clock, peaks at this circadian time. Consequently, the TS and NTS of many genes are repaired out of phase. As most cancers are thought to have defective circadian rhythms, these results suggest that future research on timed dosage of cisplatin could potentially reduce damage to healthy tissue and improve its therapeutic index.

ACS Style

Yanyan Yang; Ogun Adebali; Gang Wu; Christopher P. Selby; Yi-Ying Chiou; Naim Rashid; Jinchuan Hu; John B. Hogenesch; Aziz Sancar. Cisplatin-DNA adduct repair of transcribed genes is controlled by two circadian programs in mouse tissues. Proceedings of the National Academy of Sciences 2018, 115, E4777 -E4785.

AMA Style

Yanyan Yang, Ogun Adebali, Gang Wu, Christopher P. Selby, Yi-Ying Chiou, Naim Rashid, Jinchuan Hu, John B. Hogenesch, Aziz Sancar. Cisplatin-DNA adduct repair of transcribed genes is controlled by two circadian programs in mouse tissues. Proceedings of the National Academy of Sciences. 2018; 115 (21):E4777-E4785.

Chicago/Turabian Style

Yanyan Yang; Ogun Adebali; Gang Wu; Christopher P. Selby; Yi-Ying Chiou; Naim Rashid; Jinchuan Hu; John B. Hogenesch; Aziz Sancar. 2018. "Cisplatin-DNA adduct repair of transcribed genes is controlled by two circadian programs in mouse tissues." Proceedings of the National Academy of Sciences 115, no. 21: E4777-E4785.

Journal article
Published: 17 April 2018 in Nature Communications
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Plants are exposed to numerous DNA-damaging stresses including the exposure to ultraviolet (UV) component of solar radiation. They employ nucleotide excision repair to remove DNA-bulky adducts and to help eliminate UV-induced DNA lesions, so as to maintain their genome integrity and their fitness. Here, we generated genome-wide single-nucleotide resolution excision repair maps of UV-induced DNA damage in Arabidopsis at different circadian time points. Our data show that the repair of UV lesions for a large fraction of the genome is controlled by the joint actions of the circadian clock and transcription by RNA polymerase II. Our findings reveal very strong repair preference for the transcribed strands of active genes in Arabidopsis, and 10–30% of the transcription-coupled repair is circadian time-dependent. This dynamic range in nucleotide excision repair levels throughout the day enables Arabidopsis to cope with the bulky DNA lesion-inducing environmental factors including UV.

ACS Style

Onur Oztas; Christopher P. Selby; Aziz Sancar; Ogun Adebali. Genome-wide excision repair in Arabidopsis is coupled to transcription and reflects circadian gene expression patterns. Nature Communications 2018, 9, 1503 .

AMA Style

Onur Oztas, Christopher P. Selby, Aziz Sancar, Ogun Adebali. Genome-wide excision repair in Arabidopsis is coupled to transcription and reflects circadian gene expression patterns. Nature Communications. 2018; 9 (1):1503.

Chicago/Turabian Style

Onur Oztas; Christopher P. Selby; Aziz Sancar; Ogun Adebali. 2018. "Genome-wide excision repair in Arabidopsis is coupled to transcription and reflects circadian gene expression patterns." Nature Communications 9, no. 1: 1503.

Journal article
Published: 26 March 2018 in Proceedings of the National Academy of Sciences
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We have adapted the eXcision Repair-sequencing (XR-seq) method to generate single-nucleotide resolution dynamic repair maps of UV-induced cyclobutane pyrimidine dimers and (6-4) pyrimidine–pyrimidone photoproducts in the Saccharomyces cerevisiae genome. We find that these photoproducts are removed from the genome primarily by incisions 13–18 nucleotides 5′ and 6–7 nucleotides 3′ to the UV damage that generate 21- to 27-nt-long excision products. Analyses of the excision repair kinetics both in single genes and at the genome-wide level reveal strong transcription-coupled repair of the transcribed strand at early time points followed by predominantly nontranscribed strand repair at later stages. We have also characterized the excision repair level as a function of the transcription level. The availability of high-resolution and dynamic repair maps should aid in future repair and mutagenesis studies in this model organism.

ACS Style

Wentao Li; Ogun Adebali; Yanyan Yang; Christopher P. Selby; Aziz Sancar. Single-nucleotide resolution dynamic repair maps of UV damage in Saccharomyces cerevisiae genome. Proceedings of the National Academy of Sciences 2018, 115, E3408 -E3415.

AMA Style

Wentao Li, Ogun Adebali, Yanyan Yang, Christopher P. Selby, Aziz Sancar. Single-nucleotide resolution dynamic repair maps of UV damage in Saccharomyces cerevisiae genome. Proceedings of the National Academy of Sciences. 2018; 115 (15):E3408-E3415.

Chicago/Turabian Style

Wentao Li; Ogun Adebali; Yanyan Yang; Christopher P. Selby; Aziz Sancar. 2018. "Single-nucleotide resolution dynamic repair maps of UV damage in Saccharomyces cerevisiae genome." Proceedings of the National Academy of Sciences 115, no. 15: E3408-E3415.

Journal article
Published: 01 November 2017 in Journal of Biological Chemistry
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Nucleotide excision repair in Escherichia coli is stimulated by transcription, specifically in the transcribed strand. Previously, it was shown that this transcription-coupled repair (TCR) is mediated by the Mfd translocase. Recently, it was proposed that in fact the majority of TCR in E. coli is catalyzed by a second pathway (“backtracking-mediated TCR”) that is dependent on the UvrD helicase and the guanosine pentaphosphate (ppGpp) alarmone/stringent response regulator. Recently, we reported that as measured by the excision repair–sequencing (XR-seq), UvrD plays no role in TCR genome-wide. Here, we tested the role of ppGpp and UvrD in TCR genome-wide and in the lacZ operon using the XR-seq method, which directly measures repair. We found that the mfd mutation abolishes TCR genome-wide and in the lacZ operon. In contrast, the relA−spoT− mutant deficient in ppGpp synthesis carries out normal TCR. We conclude that UvrD and ppGpp play no role in TCR in E. coli.

ACS Style

Ogun Adebali; Aziz Sancar; Christopher P. Selby. Mfd translocase is necessary and sufficient for transcription-coupled repair in Escherichia coli. Journal of Biological Chemistry 2017, 292, 18386 -18391.

AMA Style

Ogun Adebali, Aziz Sancar, Christopher P. Selby. Mfd translocase is necessary and sufficient for transcription-coupled repair in Escherichia coli. Journal of Biological Chemistry. 2017; 292 (45):18386-18391.

Chicago/Turabian Style

Ogun Adebali; Aziz Sancar; Christopher P. Selby. 2017. "Mfd translocase is necessary and sufficient for transcription-coupled repair in Escherichia coli." Journal of Biological Chemistry 292, no. 45: 18386-18391.

Journal article
Published: 15 September 2017 in Journal of Bacteriology
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Histidine kinases are key components of regulatory systems that enable bacteria to respond to environmental changes. Two major classes of histidine kinases are recognized on the basis of their modular design: classical (HKI) and chemotaxis specific (HKII). Recently, a new type of histidine kinase that appeared to have features of both HKIs and HKIIs was identified and termed HKIII; however, the details of HKIII's relationship to other two classes of histidine kinases, their function, and evolutionary history remain unknown. Here, we carried out genomic, phylogenetic, and protein sequence analyses that allowed us to reveal the unusual evolutionary history of this protein family, formalize its distinctive features, and propose its putative function. HKIIIs are characterized by the presence of sensory domains and the lack of a dimerization domain, which is typically present in all histidine kinases. In addition to a single-domain response regulator, HKIII signal transduction systems utilize CheX phosphatase and, in many instances, an unorthodox soluble chemoreceptor that are usual components of chemotaxis signal transduction systems. However, many HKIII genes are found in genomes completely lacking chemotaxis genes, thus decoupling their function from chemotaxis. By contrast, all HKIII-containing genomes also contain pilT , a marker gene for bacterial type IV pilus-based motility, whose regulation is proposed as a putative function for HKIII. These signal transduction systems have a narrow phyletic distribution but are present in many emerging and opportunistic pathogens, thus offering an attractive potential target for future antimicrobial drug design. IMPORTANCE Bacteria adapt to their environment and their hosts by detecting signals and regulating their cellular functions accordingly. Here, we describe a largely unexplored family of signal transduction histidine kinases, called HKIII, that have a unique modular design. While they are currently identified in a relatively short list of bacterial species, this list contains many emerging pathogens. We show that HKIIIs likely control bacterial motility across solid surfaces, which is a key virulence factor in many bacteria, including those causing severe infections. Full understanding of this putative function may help in designing effective drugs against pathogens that will not affect the majority of the beneficial human microbiome.

ACS Style

Ogun Adebali; Marharyta G. Petukh; Alexander O. Reznik; Artem V. Tishkov; Amit A. Upadhyay; Igor B. Zhulin. Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility. Journal of Bacteriology 2017, 199, 1 .

AMA Style

Ogun Adebali, Marharyta G. Petukh, Alexander O. Reznik, Artem V. Tishkov, Amit A. Upadhyay, Igor B. Zhulin. Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility. Journal of Bacteriology. 2017; 199 (18):1.

Chicago/Turabian Style

Ogun Adebali; Marharyta G. Petukh; Alexander O. Reznik; Artem V. Tishkov; Amit A. Upadhyay; Igor B. Zhulin. 2017. "Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility." Journal of Bacteriology 199, no. 18: 1.

Review
Published: 01 September 2017 in Journal of Biological Chemistry
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Nucleotide excision repair is a major DNA repair mechanism in all cellular organisms. In this repair system, the DNA damage is removed by concerted dual incisions bracketing the damage and at a precise distance from the damage. Here, we review the basic mechanisms of excision repair in Escherichia coli and humans and the recent genome-wide mapping of DNA damage and repair in these organisms at single-nucleotide resolution.

ACS Style

Jinchuan Hu; Christopher P. Selby; Sheera Adar; Ogun Adebali; Aziz Sancar. Molecular mechanisms and genomic maps of DNA excision repair in Escherichia coli and humans. Journal of Biological Chemistry 2017, 292, 15588 -15597.

AMA Style

Jinchuan Hu, Christopher P. Selby, Sheera Adar, Ogun Adebali, Aziz Sancar. Molecular mechanisms and genomic maps of DNA excision repair in Escherichia coli and humans. Journal of Biological Chemistry. 2017; 292 (38):15588-15597.

Chicago/Turabian Style

Jinchuan Hu; Christopher P. Selby; Sheera Adar; Ogun Adebali; Aziz Sancar. 2017. "Molecular mechanisms and genomic maps of DNA excision repair in Escherichia coli and humans." Journal of Biological Chemistry 292, no. 38: 15588-15597.

Research article
Published: 12 June 2017 in Proceedings of the National Academy of Sciences
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Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, is the major cause of lung cancer. BaP forms covalent DNA adducts after metabolic activation and induces mutations. We have developed a method for capturing oligonucleotides carrying bulky base adducts, including UV-induced cyclobutane pyrimidine dimers (CPDs) and BaP diol epoxide-deoxyguanosine (BPDE-dG), which are removed from the genome by nucleotide excision repair. The isolated oligonucleotides are ligated to adaptors, and after damage-specific immunoprecipitation, the adaptor-ligated oligonucleotides are converted to dsDNA with an appropriate translesion DNA synthesis (TLS) polymerase, followed by PCR amplification and next-generation sequencing (NGS) to generate genome-wide repair maps. We have termed this method translesion excision repair-sequencing (tXR-seq). In contrast to our previously described XR-seq method, tXR-seq does not depend on repair/removal of the damage in the excised oligonucleotides, and thus it is applicable to essentially all DNA damages processed by nucleotide excision repair. Here we present the excision repair maps for CPDs and BPDE-dG adducts generated by tXR-Seq for the human genome. In addition, we report the sequence specificity of BPDE-dG excision repair using tXR-seq. Significance Benzo[a]pyrene (BaP) is a widespread potent carcinogen found in food, coal tar, cigarette smoke, and industrial smoke. Cigarette smoking is the leading cause of lung cancer, and the mutagenesis in smoking-associated lung cancer is determined by multiple factors, including nucleotide excision repair. We have developed a general method for genome-wide mapping of nucleotide excision repair at single-nucleotide resolution and applied it to generate repair maps of UV- and BaP-induced DNA damage in human. Results show a novel sequence specificity of BaP diol epoxide-deoxyguanosine repair. This general method can be used to study repair of all types of DNA damages that undergo nucleotide excision repair.

ACS Style

Wentao Li; Jinchuan Hu; Ogun Adebali; Sheera Adar; Yanyan Yang; Yi-Ying Chiou; Aziz Sancar. Human genome-wide repair map of DNA damage caused by the cigarette smoke carcinogen benzo[a]pyrene. Proceedings of the National Academy of Sciences 2017, 114, 201706021 -6757.

AMA Style

Wentao Li, Jinchuan Hu, Ogun Adebali, Sheera Adar, Yanyan Yang, Yi-Ying Chiou, Aziz Sancar. Human genome-wide repair map of DNA damage caused by the cigarette smoke carcinogen benzo[a]pyrene. Proceedings of the National Academy of Sciences. 2017; 114 (26):201706021-6757.

Chicago/Turabian Style

Wentao Li; Jinchuan Hu; Ogun Adebali; Sheera Adar; Yanyan Yang; Yi-Ying Chiou; Aziz Sancar. 2017. "Human genome-wide repair map of DNA damage caused by the cigarette smoke carcinogen benzo[a]pyrene." Proceedings of the National Academy of Sciences 114, no. 26: 201706021-6757.

Journal article
Published: 12 June 2017 in Proceedings of the National Academy of Sciences
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Formation and repair of UV-induced DNA damage in human cells are affected by cellular context. To study factors influencing damage formation and repair genome-wide, we developed a highly sensitive single-nucleotide resolution damage mapping method [high-sensitivity damage sequencing (HS–Damage-seq)]. Damage maps of both cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] from UV-irradiated cellular and naked DNA revealed that the effect of transcription factor binding on bulky adducts formation varies, depending on the specific transcription factor, damage type, and strand. We also generated time-resolved UV damage maps of both CPDs and (6-4)PPs by HS–Damage-seq and compared them to the complementary repair maps of the human genome obtained by excision repair sequencing to gain insight into factors that affect UV-induced DNA damage and repair and ultimately UV carcinogenesis. The combination of the two methods revealed that, whereas UV-induced damage is virtually uniform throughout the genome, repair is affected by chromatin states, transcription, and transcription factor binding, in a manner that depends on the type of DNA damage. Significance Nucleotide excision repair removes DNA damage caused by carcinogens, such as UV and anticancer drugs, such as cisplatin. We have developed two methods, high-sensitivity damage sequencing and excision repair sequencing that map the formation and repair of damage in the human genome at single-nucleotide resolution. The combination of dynamic damage and repair maps provides a holistic perspective of UV damage and repair of the human genome and has potential applications in cancer prevention and chemotherapy.

ACS Style

Jinchuan Hu; Ogun Adebali; Sheera Adar; Aziz Sancar. Dynamic maps of UV damage formation and repair for the human genome. Proceedings of the National Academy of Sciences 2017, 114, 201706522 -6763.

AMA Style

Jinchuan Hu, Ogun Adebali, Sheera Adar, Aziz Sancar. Dynamic maps of UV damage formation and repair for the human genome. Proceedings of the National Academy of Sciences. 2017; 114 (26):201706522-6763.

Chicago/Turabian Style

Jinchuan Hu; Ogun Adebali; Sheera Adar; Aziz Sancar. 2017. "Dynamic maps of UV damage formation and repair for the human genome." Proceedings of the National Academy of Sciences 114, no. 26: 201706522-6763.