Nov 12, 2021 · We show that WRN helicase inhibitor traps WRN on chromatin leading to rapid fork stalling and nucleolytic degradation of unprotected forks by MRE11, resulting in MUS81-dependent double-strand...

Mar 3, 2019 · 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.

Jan 6, 2024 · Loss of WRN led to higher expression of SMARCA5 in WRN KO adipocytes when compared with the expression in WT cells, as shown in Fig. 6a, b. Additionally, ectopic overexpression of WRN in the WRN KO adipocytes mitigated this dysregulation (Fig. 6 a, b).

We show that WRN helicase inhibitor traps WRN on chromatin leading to rapid fork stalling and nucleolytic degradation of unprotected forks by MRE11, resulting in MUS81-dependent double-strand breaks, elevated non-homologous end-joining and chromosomal instability.

Jan 25, 2025 · Pathogenic or null mutations in WRN helicase is a cause of premature aging disease Werner syndrome (WS). WRN is known to protect somatic cells including adult stem cells from premature senescence.

We show that WRN depletion selectively induces p53/PUMA-mediated cell death program in MMR-deficient colorectal cancer cells. The in vitro and in vivo effects of WRN depletion or inhibition are dependent on p53/PUMA-mediated apoptosis.

Werner's syndrome (WS) is a human disease with manifestations resembling premature aging. The gene defective in WS, WRN, encodes a DNA helicase. Here, we describe the generation of mice bearing a mutation that eliminates expression of the C terminus of the helicase domain of the WRN protein.

Cre-ERT2在无Tamoxifen诱导的情况下，在细胞质内处于无活性状态；当Tamoxifen诱导后，Tamoxifen的代谢产物4-OHT（雌激素类似物）与ERT结合，可使Cre-ERT2进核发挥Cre重组酶活性。 常见的基因工程小鼠可以分为两种命名方式，包括基因定点修饰的小鼠命名，比如：敲除、敲入、点突变等等，和随机转基因的小鼠命名。

May 18, 2022 · We demonstrated that WRN orchestrates TOP1cc repair through proteasome‐dependent and proteasome‐independent process, unleashing robust ssDNA generation. This in turn ensues signal transduction for CHK1 mediated NF‐κB‐activation through IκBα‐degradation and nuclear localization of p65 protein.

Dec 7, 2018 · We found that MDM2 can promote cellular senescence by modulating WRN stability. Werner syndrome (WS), caused by mutations of the WRN gene, is an autosomal recessive disease, which is...