Rad52 forms DNA repair and recombination centers during S phase

Proceedings of the National Academy of Sciences of the United States of America - Tập 98 Số 15 - Trang 8276-8282 - 2001
Michael Lisby1, Rodney Rothstein1, Uffe Hasbro Mortensen1
1Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, 701 West 168th Street, New York, NY 10032-2704; and Center for Process Biotechnology, BioCentrum-DTU, Technical University of Denmark, Building 223, DK-2800 Lyngby, Denmark

Tóm tắt

Maintenance of genomic integrity and stable transmission of genetic information depend on a number of DNA repair processes. Failure to faithfully perform these processes can result in genetic alterations and subsequent development of cancer and other genetic diseases. In the eukaryote Saccharomyces cerevisiae , homologous recombination is the major pathway for repairing DNA double-strand breaks. The key role played by Rad52 in this pathway has been attributed to its ability to seek out and mediate annealing of homologous DNA strands. In this study, we find that S. cerevisiae Rad52 fused to green fluorescent protein (GFP) is fully functional in DNA repair and recombination. After induction of DNA double-strand breaks by γ - irradiation, meiosis, or the HO endonuclease, Rad52-GFP relocalizes from a diffuse nuclear distribution to distinct foci. Interestingly, Rad52 foci are formed almost exclusively during the S phase of mitotic cells, consistent with coordination between recombinational repair and DNA replication. This notion is further strengthened by the dramatic increase in the frequency of Rad52 focus formation observed in a pol12 - 100 replication mutant and a mec1 DNA damage checkpoint mutant. Furthermore, our data indicate that each Rad52 focus represents a center of recombinational repair capable of processing multiple DNA lesions.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 98 Số 15

8276-8282

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