title: Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein.
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.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA, Department of Microbiology & Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA and Department of Epidemiology & Public Health, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Anaid
authors.initials: A
authors.lastname: Benitez
authors.forename: Fenghua
authors.initials: F
authors.lastname: Yuan
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakajima
authors.forename: Leizhen
authors.initials: L
authors.lastname: Wei
authors.forename: Liangyue
authors.initials: L
authors.lastname: Qian
authors.forename: Richard
authors.initials: R
authors.lastname: Myers
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Lan
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D052217:Fanconi Anemia Complementation Group A Protein / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008730:Methoxsalen / Q000494:pharmacology
chemical_list: D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein; C507947:Eme1 protein, human; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C498772:MUS81 protein, human; D008730:Methoxsalen