Jason Luke Parsons

Prof. Jason Luke Parsons

Department of Molecular and Clinical Cancer Medicine, Cancer Research Centre, University of Liverpool, 200 London Road, Liverpool L3 9TA, UK
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Research Focus & Metrics

Academic Career Length

29Years (1998-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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1 November 2011 in Chemistry & Biology
Verified
Journal Article
Closed access
MAMikael Altun
Mikael Altun
HKHolger B. Kramer
Holger B. Kramer
LWLianne Willems
Lianne Willems
JMJeffrey L. McDermott
Jeffrey L. McDermott
CLCraig A. Leach
Craig A. Leach
BKBenedikt Kessler
Benedikt Kessler

Verified
Journal Article
Open access
PDF file
JHJonathan Hughes
Jonathan Hughes
Jason Luke ParsonsJason Luke Parsons
Jason Luke Parsons
FLASH radiotherapy is the delivery of ultra-high dose rate radiation several orders of magnitude higher than what is currently used in conventional clinical radiotherapy, and has the potential to revolutionize the future of cancer treatment. FLASH radiotherapy induces a phenomenon known as the FLASH effect, whereby the ultra-high dose rate radiation reduces the normal tissue toxicities commonly associated with conventional radiotherapy, while still maintaining local tumor control. The underlying mechanism(s) responsible for the FLASH effect are yet to be fully elucidated, but a prominent role for oxygen tension and reactive oxygen species production is the most current valid hypothesis. The FLASH effect has been confirmed in many studies in recent years, both in vitro and in vivo, with even the first patient with T-cell cutaneous lymphoma being treated using FLASH radiotherapy. However, most of the studies into FLASH radiotherapy have used electron beams that have low tissue penetration, which presents a limitation for translation into clinical practice. A promising alternate FLASH delivery method is via proton beam therapy, as the dose can be deposited deeper within the tissue. However, studies into FLASH protons are currently sparse. This review will summarize FLASH radiotherapy research conducted to date and the current theories explaining the FLASH effect, with an emphasis on the future potential for FLASH proton beam therapy.

19 August 2005 in Nucleic Acids Research
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Journal Article
Open access
Srinivasan MadhusudanSrinivasan Madhusudan
Srinivasan Madhusudan
FSF. Smart
F. Smart
PSP. Shrimpton
P. Shrimpton
Jason Luke ParsonsJason Luke Parsons
Jason Luke Parsons
LGL. Gardiner
L. Gardiner
IHI. D. Hickson
I. D. Hickson
The base excision repair (BER) pathway is essential for the removal of DNA bases damaged by alkylation or oxidation. A key step in BER is the processing of an apurinic/apyrimidinic (AP) site intermediate by an AP endonuclease. The major AP endonuclease in human cells (APE1, also termed HAP1 and Ref-1) accounts for >95% of the total AP endonuclease activity, and is essential for the protection of cells against the toxic effects of several classes of DNA damaging agents. Moreover, APE1 overexpression has been linked to radio- and chemo-resistance in human tumors. Using a newly developed high-throughput screen, several chemical inhibitors of APE1 have been isolated. Amongst these, CRT0044876 was identified as a potent and selective APE1 inhibitor. CRT0044876 inhibits the AP endonuclease, 3'-phosphodiesterase and 3'-phosphatase activities of APE1 at low micromolar concentrations, and is a specific inhibitor of the exonuclease III family of enzymes to which APE1 belongs. At non-cytotoxic concentrations, CRT0044876 potentiates the cytotoxicity of several DNA base-targeting compounds. This enhancement of cytotoxicity is associated with an accumulation of unrepaired AP sites. In silico modeling studies suggest that CRT0044876 binds to the active site of APE1. These studies provide both a novel reagent for probing APE1 function in human cells, and a rational basis for the development of APE1-targeting drugs for antitumor therapy.

1 March 2012 in Molecular Cell
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Journal Article
Open access
SKSvetlana V. Khoronenkova
Svetlana V. Khoronenkova
IDIrina I. Dianova
Irina I. Dianova
NTNicola Ternette
Nicola Ternette
BKBenedikt Kessler
Benedikt Kessler
Jason Luke ParsonsJason Luke Parsons
Jason Luke Parsons
GDGrigory L. Dianov
Grigory L. Dianov
The deubiquitylation enzyme USP7/HAUSP plays a major role in regulating genome stability and cancer prevention by controlling the key proteins involved in the DNA damage response. Despite this important role in controlling other proteins, USP7 itself has not been recognized as a target for regulation. Here, we report that USP7 regulation plays a central role in DNA damage signal transmission. We find that stabilization of Mdm2, and correspondingly p53 downregulation in unstressed cells, is accomplished by a specific isoform of USP7 (USP7S), which is phosphorylated at serine 18 by the protein kinase CK2. Phosphorylation stabilizes USP7S and thus contributes to Mdm2 stabilization and downregulation of p53. After ionizing radiation, dephosphorylation of USP7S by the ATM-dependent protein phosphatase PPM1G leads to USP7S downregulation, followed by Mdm2 downregulation and accumulation of p53. Our findings provide a quantitative transmission mechanism of the DNA damage signal to coordinate a p53-dependent DNA damage response.

1 February 2008 in Molecular Cell
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Journal Article
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Jason Luke ParsonsJason Luke Parsons
Jason Luke Parsons
PTPhillip S. Tait
Phillip S. Tait
DFDavid Finch
David Finch
IDIrina I. Dianova
Irina I. Dianova
SASarah Allinson
Sarah Allinson
GDGrigory L. Dianov
Grigory L. Dianov

1 May 2016 in Molecular and Cellular Biology
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Journal Article
Closed access
PDF file
RCRachel J. Carter
Rachel J. Carter
Jason Luke ParsonsJason Luke Parsons
Jason Luke Parsons
Base excision repair (BER) is an essential DNA repair pathway involved in the maintenance of genome stability, and thus in the prevention of human diseases, such as premature aging, neurodegenerative diseases and cancer. Protein post-translational modifications (PTMs), including acetylation, methylation, phosphorylation, SUMOylation and ubiquitylation, have emerged as important contributors in controlling cellular BER protein levels, enzymatic activities, protein-protein interactions and protein cellular localisation. These PTMs therefore play key roles in regulating the BER pathway, and are consequently crucial for co-ordinating an efficient cellular DNA damage response. In this review, we summarise the presently available data on characterised PTMs of key BER proteins, and the functional consequences of these modifications at the protein level, but also the impact on BER in vitro and in vivo.