Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein

Anaid Benitez, Fenghua Yuan, Satoshi Nakajima, Leizhen Wei, Liangyue Qian, Richard Myers, Jennifer J. Hu, Li Lan, Yanbin Zhang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

MUS81-EME1 is a DNA endonuclease involved in replication-coupled repair of DNA interstrand cross-links (ICLs). A prevalent hypothetical role of MUS81-EME1 in ICL repair is to unhook the damage by incising the leading strand at the 3′ side of an ICL lesion. In this study, we report that purified MUS81-EME1 incises DNA at the 5′ side of a psoralen ICL residing in fork structures. Intriguingly, ICL repair protein, Fanconi anemia complementation group A protein (FANCA), greatly enhances MUS81-EME1-mediated ICL incision. On the contrary, FANCA exhibits a two-phase incision regulation when DNA is undamaged or the damage affects only one DNA strand. Studies using truncated FANCA proteins indicate that both the N- and C-moieties of the protein are required for the incision regulation. Using laser-induced psoralen ICL formation in cells, we find that FANCA interacts with and recruits MUS81 to ICL lesions. This report clarifies the incision specificity of MUS81-EME1 on ICL damage and establishes that FANCA regulates the incision activity of MUS81-EME1 in a damage-dependent manner.

Original languageEnglish (US)
Pages (from-to)1671-1683
Number of pages13
JournalNucleic acids research
Volume42
Issue number3
DOIs
StatePublished - Feb 1 2014

ASJC Scopus subject areas

  • Genetics

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