BRCA1 downregulates the kinase activity of Polo-like kinase 1 in response to replication stress

Jianqiu Zou, Khosrow Rezvani, Hongmin Wang, Kyung S. Lee, Dong Zhang

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

In response to DNA damage or replication stress, proliferating cells are arrested at different cell cycle stages for DNA repair by downregulating the activity of both the cyclin-dependent kinases (CDKs) and other important cell cycle kinases, including Polo-like kinase 1 (PLK1). The signaling pathway to inhibit CDKs is relatively well understood, and breast cancer gene 1 (BRCA1) and other DNA damage response (DDR) factors play a key role in this process. However, the DNA damageinduced inhibition of PLK1 is still largely a mystery. Here we show that DNA damage and replication stress stimulate the association between BRCA1 and PLK1. Most importantly, we demonstrate that BRCA1 downregulates the kinase activity of PLK1 by modulating the dynamic interactions of Aurora A, hBora, and PLK1. Together with previous findings, we propose that in response to replication stress and DNA damage, BRCA1 plays a critical role in downregulating the kinase activity of both CDKs and PLK1.

Original languageEnglish (US)
Pages (from-to)2255-2265
Number of pages11
JournalCell Cycle
Volume12
Issue number14
DOIs
StatePublished - Jul 15 2013
Externally publishedYes

Keywords

  • BRCA1
  • DNA damage
  • PLK1
  • Replication stress

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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