Regulation of Chromatin Architecture by the PWWP Domain-Containing DNA Damage-Responsive Factor EXPAND1/MUM1

Michael S.Y. Huen, Jun Huang, Justin W.C. Leung, Shirley M.H. Sy, Ka Man Leung, Yick Pang Ching, Sai Wah Tsao, Junjie Chen

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Dynamic changes of chromatin structure facilitate diverse biological events, including DNA replication, repair, recombination, and gene transcription. Recent evidence revealed that DNA damage elicits alterations to the chromatin to facilitate proper checkpoint activation and DNA repair. Here we report the identification of the PWWP domain-containing protein EXPAND1/MUM1 as an architectural component of the chromatin, which in response to DNA damage serves as an accessory factor to promote cell survival. Depletion of EXPAND1/MUM1 or inactivation of its PWWP domain resulted in chromatin compaction. Upon DNA damage, EXPAND1/MUM1 rapidly concentrates at the vicinity of DNA damage sites via its direct interaction with 53BP1. Ablation of this interaction impaired damage-induced chromatin decondensation, which is accompanied by sustained DNA damage and hypersensitivity to genotoxic stress. Collectively, our study uncovers a chromatin-bound factor that serves an accessory role in coupling damage signaling with chromatin changes in response to DNA damage.

Original languageEnglish (US)
Pages (from-to)854-864
Number of pages11
JournalMolecular Cell
Volume37
Issue number6
DOIs
StatePublished - Mar 26 2010
Externally publishedYes

Keywords

  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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