Published online 14 October 2004
Nucleic Acids Research, Vol. 32 No. 18 © Oxford University Press 2004; all rights reserved
DNA repair by a Rad22–Mus81-dependent pathway that is independent of Rhp51
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
* To whom correspondence should be addressed. Tel: +44 1865 275192; Fax: +44 1865 275297; Email: matthew.whitby{at}bioch.ox.ac.uk
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
Received June 8, 2004; Revised and Accepted September 9, 2004
In budding yeast most Rad51-dependent and -independent recombination depends on Rad52. In contrast, its homologue in fission yeast, Rad22, was assumed to play a less critical role possibly due to functional redundancy with another Rad52-like protein Rti1. We show here that this is not the case. Rad22 like Rad52 plays a central role in recombination being required for both Rhp51-dependent and -independent events. Having established this we proceed to investigate the involvement of the Mus81–Eme1 endonuclease in these pathways. Mus81 plays a relatively minor role in the Rhp51-dependent repair of DNA damage induced by ultraviolet light. In contrast Mus81 has a key role in the Rad22-dependent (Rhp51-independent) repair of damage induced by camptothecin, hydroxyurea and methyl-methanesulfonate. Furthermore, spontaneous intrachromosomal recombination that gives rise to deletion recombinants is impaired in a mus81 mutant. From these data we propose that a Rad22–Mus81-dependent (Rhp51-independent) pathway is an important mechanism for the repair of DNA damage in fission yeast. Consistent with this we show that in vitro Rad22 can promote strand invasion to form a D-loop that can be cleaved by Mus81.
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