Sumoylation of MDC1 is important for proper DNA damage response

Kuntian Luo, Haoxing Zhang, Liewei Wang, Jian Yuan, Zhenkun Lou

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

In response to DNA damage, many DNA damage factors, such as MDC1 and 53BP1, redistribute to sites of DNA damage. The mechanism governing the turnover of these factors at DNA damage sites, however, remains enigmatic. Here, we show that MDC1 is sumoylated following DNA damage, and the sumoylation of MDC1 at Lys1840 is required for MDC1 degradation and removal of MDC1 and 53BP1 from sites of DNA damage. Sumoylated MDC1 is recognized and ubiquitinated by the SUMO-targeted E3 ubiquitin ligase RNF4. Mutation of the MDC1 Lys 1840 (K1840R) results in impaired CtIP, replication protein A, and Rad51 accumulation at sites of DNA damage and defective homologous recombination (HR). The HR defect caused by MDC1K1840R mutation could be rescued by 53BP1 downregulation. These results reveal the intricate dynamics governing the assembly and disassembly of DNA damage factors at sites of DNA damage for prompt response to DNA damage.

Original languageEnglish (US)
Pages (from-to)3008-3019
Number of pages12
JournalEMBO Journal
Volume31
Issue number13
DOIs
StatePublished - Jul 4 2012

Keywords

  • MDC1
  • RNF4
  • homologous recombination
  • sumoylation
  • ubiquitination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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