Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases

Abstract

DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination and repair. In the yeast Saccharomyces cerevisiae, the absence of the Sgs1 helicase results in genomic instability and accelerated ageing1,2,3,4. In human cells, mutations in orthologues of SGS1 lead to Bloom (BS), Werner (WS) or Rothmund-Thomson (RTS) syndromes, which are rare, autosomal recessive diseases characterized by genetic instability associated with cancer predisposition5,6,7. Although data concerning these human diseases are accumulating, there is still no clear idea of the function of the proteins involved. Here we show that sgs1Δ mutants are deficient in DNA repair and are defective for induced recombination events that involve homologous chromosomes. The role of homologous recombination is further evidenced in haploid cells in which both Sgs1p and Srs2p are absent. Yeast SRS2 encodes another DNA helicase involved in the maintenance of genome integrity8,9,10. Our data suggest that some defects observed in BS, WS or RTS are the consequence of unrestrained recombination.

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Figure 1: Effects of irradiation on survival and heteroallelic recombination of sgs1Δ mutants.
Figure 2: Tetrad dissections of W303 derivatives heterozygous for srs2::HIS3 , sgs1::URA3 and either rad51::LEU2 (D28), rad55::LEU2 (D29) or rad57::LEU2 (D30).
Figure 3: Comparison of spore colony growth on YPD medium.

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Acknowledgements

We thank E. Coïc, X. Veaute and J. Smith for commenting on the manuscript; and R. Borts for constructing the lys2 heteroalleles in the W303 background. This work was supported by le Commissariat à l'Energie Atomique, le Centre National pour la Recherche Scientifique, le Ministère de l'Education Nationale, de la Recherche et de la Technologie and Electricité de France.

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Correspondence to Serge Gangloff or Francis Fabre.

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