Reference - PMID:23982516 - A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes.
Reference summary
- PubMed ID
- PMID:23982516
- Title
- A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes.
- Authors
- Fadden AJ, Schalbetter S, Bowles M, Harris R, Lally J, Carr AM, McDonald NQ
- Citation
- Nucleic Acids Res 2013 Nov;41(21):9741-52
- Publication year
- 2013
- Abstract
- The MUS81-EME1 endonuclease maintains metazoan genomic integrity by cleaving branched DNA structures that arise during the resolution of recombination intermediates. In humans, MUS81 also forms a poorly characterized complex with EME2. Here, we identify and determine the structure of a winged helix (WH) domain from human MUS81, which binds DNA. WH domain mutations greatly reduce binding of the isolated domain to DNA and impact on incision activity of MUS81-EME1/EME2 complexes. Deletion of the WH domain reduces the endonuclease activity of both MUS81-EME1 and MUS81-EME2 complexes, and incisions made by MUS81-EME2 are made closer to the junction on substrates containing a downstream duplex, such as fork structures and nicked Holliday junctions. WH domain mutation or deletion in Schizosaccharomyces pombe phenocopies the DNA-damage sensitivity of strains deleted for mus81. Our results indicate an important role for the WH domain in both yeast and human MUS81 complexes.
