ATR protects ongoing and newly assembled DNA replication forks …
2023年7月25日 · Here, we combine four distinct assays to analyze ATR functions at ongoing and newly assembled replication forks upon replication inhibition by hydroxyurea. At ongoing forks, ATR inhibitor (ATRi) increases MRE11- and EXO1-mediated nascent DNA degradation from PrimPol-generated, single-stranded DNA (ssDNA) gaps.
ATR blocks telomerase from converting DNA breaks into telomeres
2024年2月15日 · RPA depletion with small interfering RNA (siRNA) elicited a 2.5-fold increase in neotelomere formation (Fig. 4, C and D), and treatment with two ATR inhibitors (VE-821 and gartisertib/M4344) nearly tripled the frequency of the events, whereas inhibitors of DNA-PKcs or ATM had no effect . ATRi only slightly increased the S-phase index of the ...
ATR inhibition activates cancer cell cGAS/STING-interferon
2024年9月27日 · The PD-L1 expression in H1048 increased with genetic knockdown of ATR with siRNA (fig. S3E). These results demonstrate that ATRi activates the innate immune cGAS/STING pathway and induces expression of type I IFNs, chemokines (CXCL10 and CCL5) via induction of the cGAS/STING pathway, and PD-L1 expression in SCLC cells.
Acetylation regulates ribonucleotide reductase activity and …
2019年7月19日 · ATR-mediated RRM2 phosphorylation at S150 enhances its association with Sirt2 and facilitates RRM2 deacetylation. Pharmacological manipulation of K95 acetylation may represent a viable strategy...
PHF8-promoted TOPBP1 demethylation drives ATR activation …
The checkpoint kinase ATR [ATM (ataxia-telangiectasia mutated) and rad3-related] is a master regulator of DNA damage response. Yet, how ATR activity is regulated remains to be investigated. We report here that histone demethylase PHF8 (plant homeodomain finger protein 8) plays a key role in ATR activation and replication stress response.
ATR and p-ATR are emerging prognostic biomarkers and DNA …
2020年12月23日 · ATR-specific small interfering RNA (siRNA) and ATR inhibitor VE-822 were applied to determine the effects of ATR inhibition on ovarian cancer cell proliferation, apoptosis, and DNA damage. ATR expression and the associated proteins of the ATR/Chk1 pathway in ovarian cancer cell lines were evaluated by Western blotting.
DNA double-strand break repair pathway regulates PD-L1 ... - Nature
2017年11月24日 · This upregulation requires ATM/ATR/Chk1 kinases. Using an siRNA library targeting DSB repair genes, we discover that BRCA2 depletion enhances Chk1-dependent PD-L1 upregulation after X-rays or...
Differential roles of ATR and ATM in p53, Chk1, and histone H2AX ...
We have investigated the effect of hyperoxia on DNA damage signaling and show that hyperoxia is a unique stress that activates the ataxia telangiectasia mutant (ATM)-and Rad3-related protein kinase (ATR)-dependent p53 phosphorylations (Ser6, −15, −37, and −392), phosphorylation of histone H2AX (Ser139), and phosphorylation of checkpoint kinase 1...
Combined PARP and ATR inhibition potentiates genome
2020年5月23日 · Combination of S-1 and the oral ATR inhibitor ceralasertib is effective against pancreatic cancer cells. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib is FDA approved for the ...
ATM and ATR Signaling Regulate the Recruitment of Human
Depletion of ATM and ATR using small interfering RNA (siRNA) resulted in reduction of levels of each protein by ∼95% and ∼80%, respectively (Figure 1B), without causing significant perturbations in progression of the cells through the cell cycle (Figure S1A).