Recruitment of proteins to DNA double-strand breaks: MDC1 directly recruits RAP80

Carmit Strauss, Michal Goldberg

Research output: Contribution to journalReview articlepeer-review

Abstract

DNA double-strand breaks (DSBs) are the most severe type of DNA damage. Occurrence of DSBs in the cell activates the DNA damage response (DDR), which involves signaling cascades that sense and respond to the damage. Promptly after DSB induction, DDR proteins accumulate surrounding both DNA ends and form microscopically-visible foci. Recently, we demonstrated that the key DDR protein MDC1 directly binds RAP80, an additional DDR protein that recruits BRCA1 to DSBs. We provided evidences that the MDC1-RAP80 interaction depends on a ubiquitylation event on K-1977 of MDC1. However, it remained unknown whether K-1977 of MDC1 is required for the recruitment of RAP80 to DSBs. Here we show that K-1977 of MDC1 is necessary for focus formation by RAP80. Nevertheless, it has no effect on focus formation by γH2AX, MDC1 or 53BP1. The results imply a role for the MDC1-RAP80 interaction in focus formation by the RAP80-BRCA1 complex. In light of these recent results, we discuss several aspects of the complexity of focus formation and present a model for the involvement of individual and complex recruitment mechanisms in focus formation.

Original languageAmerican English
Pages (from-to)2850-2857
Number of pages8
JournalCell Cycle
Volume10
Issue number17
DOIs
StatePublished - 1 Sep 2011

Keywords

  • DNA damage response
  • DNA double-strand break
  • Focus formation
  • MDC1
  • RAP80

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Recruitment of proteins to DNA double-strand breaks: MDC1 directly recruits RAP80'. Together they form a unique fingerprint.

Cite this