Article abstract
Nature Structural & Molecular Biology 14, 1096 - 1104 (2007)
Published online: 14 October 2007 | doi:10.1038/nsmb1313
The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks
Katsuhiro Hanada1,2, Magda Budzowska1, Sally L Davies2, Ellen van Drunen3, Hideo Onizawa1, H Berna Beverloo3, Alex Maas1, Jeroen Essers1,4, Ian D Hickson2 & Roland Kanaar1,4
Abstract
Faithful duplication of the genome requires structure-specific endonucleases such as the RuvABC complex in Escherichia coli. These enzymes help to resolve problems at replication forks that have been disrupted by DNA damage in the template. Much less is known about the identities of these enzymes in mammalian cells. Mus81 is the catalytic component of a eukaryotic structure-specific endonuclease that preferentially cleaves branched DNA substrates reminiscent of replication and recombination intermediates. Here we explore the mechanisms by which Mus81 maintains chromosomal stability. We found that Mus81 is involved in the formation of double-strand DNA breaks in response to the inhibition of replication. Moreover, in the absence of chromosome processing by Mus81, recovery of stalled DNA replication forks is attenuated and chromosomal aberrations arise. We suggest that Mus81 suppresses chromosomal instability by converting potentially detrimental replication-associated DNA structures into intermediates that are more amenable to DNA repair.
- Department of Cell Biology & Genetics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
- Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
- Department of Clinical Genetics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
- Department of Radiation Oncology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Correspondence to: Roland Kanaar1,4 e-mail: r.kanaar@erasmusmc.nl
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