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 Hu, Li Lan, Yanbin Zhang

Research output: Contribution to journalArticle

9 Citations (Scopus)

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
Pages (from-to)1671-1683
Number of pages13
JournalNucleic Acids Research
Volume42
Issue number3
DOIs
StatePublished - Feb 1 2014

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Fanconi Anemia Complementation Group A Protein
Ficusin
DNA
Deoxyribonuclease I
Protein C
DNA Repair
Lasers

ASJC Scopus subject areas

  • Genetics

Cite this

Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein. / Benitez, Anaid; Yuan, Fenghua; Nakajima, Satoshi; Wei, Leizhen; Qian, Liangyue; Myers, Richard; Hu, Jennifer; Lan, Li; Zhang, Yanbin.

In: Nucleic Acids Research, Vol. 42, No. 3, 01.02.2014, p. 1671-1683.

Research output: Contribution to journalArticle

Benitez, Anaid ; Yuan, Fenghua ; Nakajima, Satoshi ; Wei, Leizhen ; Qian, Liangyue ; Myers, Richard ; Hu, Jennifer ; Lan, Li ; Zhang, Yanbin. / Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein. In: Nucleic Acids Research. 2014 ; Vol. 42, No. 3. pp. 1671-1683.
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