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Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae

Nature volume 388, pages 900–903 (1997)Cite this article

Abstract

DNA double-strand breaks are repaired by homologous recombination or DNA end-joining, but the latter process often causes illegitimate recombination and chromosome rearrangements. One of the factors involved in the end-joining process is Hdf1, a yeast homologue of Ku protein1,2,3,4. We used the yeast two-hybrid assay to show that Hdf1 interacts with Sir4, which is involved in transcriptional silencing at telomeres and HM loci5,6. Analyses of sir4 mutants showed that Sir4 is required for deletion by illegitimate recombination and DNA end-joining in the pathway involving Hdf1. Sir2 and Sir3, but not Sir1, were also found to participate in these processes. Furthermore, mutations of the SIR2, SIR3 and SIR4 genes conferred increased sensitivity to γ-radiation in a genetic background with a mutation of the RAD52 gene, which is essential for double-strand break repair mediated by homologous recombination. These results indicate that Sir proteins are involved in double-strand break repair mediated by end-joining. We propose that Sir proteins act with Hdf1 to alter broken DNA ends to create an inactivated chromatin structure that is essential for the rejoining of DNA ends.

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Figure 1: Deficiency in deletion formation and end-joining in sir mutants.
Figure 2: Sensitivity of sir and rad52 double mutants to γ-irradiation.

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Acknowledgements

We thank S. Fields, S. M. Hollenberg, K. Johzuka, I. Kobayashi, A. Miyajima, J. Rine and J. W. Szostak for providing plasmids and strains, and K. Johzuka for advice on the two-hybrid assay. This work was supported in part by grants to Y.T., J.K. and H.I. from the Ministry of Education, Science, Sports, and Culture of Japan. Y.T. was supported by a postdoctoral fellowship of the Japan Society for the Promotion of Science.

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  1. Department of Molecular Biology, Institute of Medical Science, University of Tokyo, P.O. Takanawa, Tokyo, 108, Japan

    Yasumasa Tsukamoto, Jun-ichi Kato & Hideo Ikeda

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  1. Yasumasa Tsukamoto
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  2. Jun-ichi Kato
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  3. Hideo Ikeda
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Correspondence to Hideo Ikeda.

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Tsukamoto, Y., Kato, Ji. & Ikeda, H. Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae. Nature 388, 900–903 (1997). https://doi.org/10.1038/42288

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