USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM

Chenming Wu, Yiming Chang, Junliang Chen, Yang Su, Lei Li, Yuping Chen, Yunhui Li, Jinhuan Wu, Jinzhou Huang, Fei Zhao, Wenrui Wang, Hui Yin, Shunli Wang, Mingpeng Jin, Zhenkun Lou, Wei Guo Zhu, Kuntian Luo, Jie Zhang, Jian Yuan

Research output: Contribution to journalArticlepeer-review


The human RecQ helicase BLM is involved in the DNA damage response, DNA metabolism, and genetic stability. Loss of function mutations in BLM cause the genetic instability/cancer predisposition syndrome Bloom syndrome. However, the molecular mechanism underlying the regulation of BLM in cancers remains largely elusive. Here, we demonstrate that the deubiquitinating enzyme USP37 interacts with BLM and that USP37 deubiquitinates and stabilizes BLM, thereby sustaining the DNA damage response (DDR). Mechanistically, DNA double-strand breaks (DSB) promotes ATM phosphorylation of USP37 and enhances the binding between USP37 and BLM. Moreover, knockdown of USP37 increases BLM polyubiquitination, accelerates its proteolysis, and impairs its function in DNA damage response. This leads to enhanced DNA damage and sensitizes breast cancer cells to DNA-damaging agents in both cell culture and in vivo mouse models. Collectively, our results establish a novel molecular mechanism for the USP37-BLM axis in regulating DSB repair with an important role in chemotherapy and radiotherapy response in human cancers.

Original languageEnglish (US)
Pages (from-to)11224-11240
Number of pages17
JournalNucleic acids research
Issue number19
StatePublished - Nov 8 2021

ASJC Scopus subject areas

  • Genetics


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