A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes
Fadden, A.J. and Schalbetter, S. and Bowles, M. and Harris, R. and Lally, J. and Carr, A.M. and McDonald, Neil Q. (2013) A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes. Nucleic Acids Research , ISSN 0305-1048.
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.
Metadata
| Item Type: | Article |
|---|---|
| School: | School of Science > Biological Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 02 Sep 2013 09:10 |
| Last Modified: | 06 Dec 2016 10:43 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/8071 |
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