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: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 02 Sep 2013 09:10 |
| Last Modified: | 02 Aug 2023 17:07 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/8071 |
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