2019年4月10日 · These findings show that WRN is a synthetic lethal vulnerability and promising drug target for MSI cancers. Defects in DNA mismatch repair (MMR) promote a hypermutable state with frequent...

2024年4月24日 · Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative...

2024年4月24日 · Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214. This compound selectively engages a cysteine (C727) located in a...

Werner syndrome protein (WRN) is a RecQ enzyme involved in the maintenance of genome integrity. Germline loss-of-function mutations in WRN led to premature aging and...

2019年3月29日 · Werner syndrome protein (WRN) is a RecQ enzyme involved in the maintenance of genome integrity. Germline loss-of-function mutations in WRN led to premature aging and predisposition to cancer. We evaluated synthetic lethal (SL) interactions between WRN and another human RecQ helicase, BLM, with DNA damage response genes in cancer cell lines.

2018年1月14日 · To further verify the role of p21 in suppressing telomere dysfunction related tumorigenesis, we knocked down p21 in non-tumorigenic immortalized cells derived from WS MEFs (mTerc -/-Wrn-/-), and found that loss of p21 could induce ALT tumorigenesis, which displayed typical smear pattern of telomere length and arc-shaped telomeric DNA. In ...

2018年1月14日 · We found that WT and Wrn-/-MEFs grew slower than p21-/-MEFs, while knock out of p21 function (p21-/-Wrn-/-) rescued the growth potential of Wrn-/-MEFs (Figure (Figure1A). 1 A). These data suggested that the growth barrier caused by dysfunction of Wrn deficiency could be overcome by the loss of p21 function.

2001年3月1日 · In contrast, the p21 null/Wrn Δhel homozygous mutant mice did not show an acceleration of tumorigenesis. These results suggest that alteration of a p53- and/or WRN-dependent pathway (possibly apoptotic) is more likely to be important in tumor progression than cell cycle checkpoint control in our mouse model.

1999年10月8日 · Overexpression of WRN leads to augmented p53-dependent transcriptional activity and induction of p21(Waf1) protein expression. These findings support the existence of a cross-talk between WRN and p53, which may be important for maintaining genomic integrity and for preventing the accumulation of aberrations that can give rise to premature ...

2023年11月23日 · The results of transcriptome sequencing revealed that WRN promoted the sensitivity of leukemia cells to the DNA damage inducer Etoposide by regulating cell cycle-related proteins, such as CDC2, cyclin B1, p16, and p21, as well as key proteins in DNA damage repair pathways, such as p53, RAD50, RAD51, and MER11.