Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein |
| |
| Authors: | Anaid Benitez Fenghua Yuan Satoshi Nakajima Leizhen Wei Liangyue Qian Richard Myers Jennifer J. Hu Li Lan Yanbin Zhang |
| |
| Affiliation: | 1.Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA, 2.Department of Microbiology & Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA and 3.Department of Epidemiology & Public Health, University of Miami Miller School of Medicine, Miami, FL 33136, USA |
| |
| 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. |
| |
| Keywords: | |
|
|
