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Article
The EMBO Journal (2001) 20, 6660–6671, doi:10.1093/emboj/20.23.6660
Fission yeast Rad50 stimulates sister chromatid recombination and links cohesion with repair
E. Hartsuiker1, E. Vaessen2, A.M. Carr1 and J. Kohli3
1 Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RR, UK
2 Institute for Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland
3 Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland

To whom correspondence should be addressed
A.M. Carr, a.m.carr@sussex.ac.uk

Received 11 April 2001; Revised 4 October 2001; Accepted 4 October 2001.
Abstract
To study the role of Rad50 in the DNA damage response, we cloned and deleted the Schizosaccharo myces pombe RAD50 homologue. The deletion is sensitive to a range of DNA-damaging agents and shows dynamic epistatic interactions with other recombination–repair genes. We show that Rad50 is necessary for recombinational repair of the DNA lesion at the mating-type locus and that rad50Delta shows slow DNA replication. We also find that Rad50 is not required for slowing down S phase in response to hydroxy urea or methyl methanesulfonate (MMS) treatment. Interestingly, in rad50Delta cells, the recombination frequency between two homologous chromosomes is increased at the expense of sister chromatid recombination. We propose that Rad50, an SMC-like protein, promotes the use of the sister chromatid as the template for homologous recombinational repair. In support of this, we found that Rad50 functions in the same pathway for the repair of MMS-induced damage as Rad21, the homologue of the Saccharomyces cerevisiae Scc1 cohesin protein. We speculate that Rad50 interacts with the cohesin complex during S phase to assist repair and possibly re-initiation of replication after replication fork collapse.
Keywords: DNA replication, Rad21, Rad50, recombinational DNA repair, sister chromatid cohesion
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