Mitotic DNA synthesis (MiDAS) serves to complete the replication of genomic loci that are not fully replicated in S phase in response to replication stress. Previous studies suggest that MiDAS might proceed via break-induced DNA replication, a sub-pathway of homologous recombination repair activated at broken or collapsed replication forks. We set out to define whether DNA double strand break end-resection factors play a role in MiDAS. Here, we show that several core end-resection factors, including MRE11, CtIP and BRCA1 are essential for MiDAS. In addition, while loss of WRN or DNA2 impairs MiDAS, there is no requirement for other known end-resection factors such as EXO1 and BLM. Moreover, both the exonuclease and the helicase activities of WRN contribute to MiDAS. Because oncogene-induced replication stress is common in cancers, targeting of WRN or other factors required for MiDAS could facilitate the development of targeted cancer therapies.

Triple-negative breast cancer (TNBC) is a type of breast tumor that currently lacks options for targeted therapy. Tremendous effort has been made to identify treatment targets for TNBC. Here, we report that the expression level of anaphase promoting complex (APC) coactivator Cdh1 in TNBC is elevated compared to that in the adjacent healthy tissues, and high levels of Cdh1 expression are correlated with poor prognoses, suggesting that Cdh1 contributes to the progression of TNBC. Interfering with the function of Cdh1 can potentiate the cytotoxic effects of PARP inhibitors against BRCA-deficient and BRCA-proficient TNBC cells through inducing DNA damage, checkpoint activation, cell cycle arrest, and apoptosis. Further investigation reveals that Cdh1 promotes BRCA1 foci formation and prevents untangled DNA entering mitosis in response to PARP inhibition (PARPi) in TNBC cells. Collectively, these results suggest that APC/Cdh1 is a potential molecular target for PARPi-based therapies against TNBCs.

The carotid artery is an important blood vessel in the human body. Its ruptures caused by accidents can be lethal cases without timely treatment. Currently, successful rescue cases have rarely been reported, hence we present the following case. A patient who was a 46-year-old male admitted due to left neck trauma that lasted almost a day. The CT angiography (CTA) of the neck showed two pseudoaneurysms: one on the anterior wall and one on the posterior wall of the carotid artery. In our case, we considered an open approach to reconstruct the carotid artery. After excision of the aneurysm, the internal carotid artery was stitched. Electrophysiological monitoring and shunt were used during the operation. The postoperative course was uneventful, and the patient remains free of symptoms. Many departments jointly and positive and effective surgical intervention are the key to reduce morbidity and mortality of carotid artery penetrating injury.

DNA Double-strand breaks (DSBs) are amongst the most cytotoxic DNA lesions. During the processing of DSBs, so-called Break-Induced RNA-DNA Hybrids (BIRDHs) are generated to promote timely DSB repair. Here, we identify the DEAD-box helicase DDX3X as a positive regulator of BIRDHs and a key factor in facilitating DSB repair via homologous recombination (HR). We demonstrate that DDX3X promotes BIRDH formation by inhibiting CST (CTC1, STN1, TEN1)-Polα fill-in synthesis, through limiting 53BP1 accumulation at DSBs in a Drosha-dependent manner. Notably, depletion of DDX3X impairs both BIRDH and BRCA1 focus formation, while disabling CST-Polα mediated fill-in synthesis in DDX3X-deficient cells restores these events. This suggests a competitive interplay between BIRDH formation and fill-in synthesis that influences DNA repair pathway choice. Consistent with a role in HR, DDX3X depletion sensitizes tumor cells to cisplatin in vitro and in vivo. We conclude that DDX3X promotes genome maintenance and cell viability following DSB formation through regulation of BIRDHs.

Circular RNAs (circRNAs) are dynamically remodeled during infection, yet how viruses exploit circRNA‐RNA binding protein (RBP) circuits remains poorly understood. Here, we report a cGLIS3 ‐IGF2BP2‐linked TNF‐α regulatory axis triggered by deltacoronavirus infection to inhibit antiviral innate immunity. The host m ⁶ A reader insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) and viral nucleocapsid (N) protein promote biogenesis of the m ⁶ A‐modified cGLIS3 by strengthening the GLIS3 exon 3 circulation. Interaction assay reveals that K‐Homology domain of IGF2BP2 or the linker region of viral protein N binds to GLIS3 pre‐mRNA to achieve cGLIS3 biogenesis, respectively. IGF2BP2 stabilizes the m ⁶ A‐modified cGLIS3 against RNase L‐mediated degradation. cGLIS3 attenuates IGF2BP2‐driven TNF‐α induction to facilitate deltacoronavirus replication by accelerating K48‐linked ubiquitin degradation of IGF2BP2. Together, our findings uncover a coronavirus‐elicited circRNA‐RBP crosstalk circuit to suppress innate immunity, establishing cGLIS3 as a mechanistically defined regulator of virus‐host interactions.