Damage-induced recombination in the yeast Saccharomyces cerevisiae

Kupiec, Martin

doi:10.1016/s0027-5107(00)00042-7

Cited by 54 publications

(27 citation statements)

References 114 publications

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“…Camptothecin induces topoisomerasemediated damage during replication, while hydroxyurea produces stalled replication forks. Mutants were also exposed for 30 min to 0.3% MMS, a radiomimetic leading to DSBs requiring homologous recombination for repair (24). All of these lesions require either the recombination or the checkpoint functions of the MRX complex (15,25,26).…”

Section: Resultsmentioning

confidence: 99%

Mutations of the Yku80 C Terminus and Xrs2 FHA Domain Specifically Block Yeast Nonhomologous End Joining

Palmbos

Daley

Wilson

2005

Molecular and Cellular Biology

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The nonhomologous end-joining (NHEJ) pathway of DNA double-strand break repair requires three protein complexes in Saccharomyces cerevisiae: MRX (Mre11-Rad50-Xrs2), Ku (Ku70-Ku80), and DNA ligase IV (Dnl4-Lif1-Nej1). Much is known about the interactions that mediate the formation of each complex, but little is known about how they act together during repair. A comprehensive yeast two-hybrid screen of the NHEJ factors of S. cerevisiae revealed all known interactions within the MRX, Ku, and DNA ligase IV complexes, as well as three additional, weaker interactions between Yku80-Dnl4, Xrs2-Lif1, and Mre11-Yku80. Individual and combined deletions of the Yku80 C terminus and the Xrs2 forkhead-associated (FHA) domain were designed based on the latter two-hybrid results. These deletions synergistically blocked NHEJ but not the telomere and recombination functions of Ku and MRX, confirming that these protein regions are functionally important specifically for NHEJ. Further mutational analysis of Yku80 identified a putative C-terminal amphipathic ␣-helix that is both required for its NHEJ function and strikingly similar to a DNA-dependent protein kinase interaction motif in human Ku80. These results identify a novel role in yeast NHEJ for the poorly characterized Ku80 C-terminal and Xrs2 FHA domains, and they suggest that redundant binding of DNA ligase IV facilitates completion of this DNA repair event.

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Section: Resultsmentioning

confidence: 99%

Mutations of the Yku80 C Terminus and Xrs2 FHA Domain Specifically Block Yeast Nonhomologous End Joining

Palmbos

Daley

Wilson

2005

Molecular and Cellular Biology

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“…Despite the long-known connection between CAs and x-rays, the underlying mechanisms that give rise to rearrangements remain unclear. In Saccharomyces cerevisiae, various types of DNA damage result in elevated levels of chromosome rearrangements including deletions, duplications, and translocations (3). These studies usually involve genetic methods that select for one type of event at specific loci.…”

mentioning

confidence: 99%

Double-strand breaks associated with repetitive DNA can reshape the genome

Argueso

Westmoreland

Mieczkowski

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

232

222

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Ionizing radiation is an established source of chromosome aberrations (CAs). Although double-strand breaks (DSBs) are implicated in radiation-induced and other CAs, the underlying mechanisms are poorly understood. Here, we show that, although the vast majority of randomly induced DSBs in G 2 diploid yeast cells are repaired efficiently through homologous recombination (HR) between sister chromatids or homologous chromosomes, Ϸ2% of all DSBs give rise to CAs. Complete molecular analysis of the genome revealed that nearly all of the CAs resulted from HR between nonallelic repetitive elements, primarily Ty retrotransposons. Nonhomologous end-joining (NHEJ) accounted for few, if any, of the CAs. We conclude that only those DSBs that fall at the 3-5% of the genome composed of repetitive DNA elements are efficient at generating rearrangements with dispersed small repeats across the genome, whereas DSBs in unique sequences are confined to recombinational repair between the large regions of homology contained in sister chromatids or homologous chromosomes. Because repeatassociated DSBs can efficiently lead to CAs and reshape the genome, they could be a rich source of evolutionary change.ectopic recombination ͉ gamma radiation ͉ genome rearrangements ͉ nonallelic homologous recombination ͉ retrotransposon

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“…In addition to HR and NHEJ, there are other DNA repair mechanisms that significantly contribute to genomic stability and, although they are not strictly DSB repair pathways, they can contribute to preventing DSB formation because they eliminate lesions that could potentially lead to replication blocks (Kupiec 2000). These mechanisms are the nucleotide excision repair (NER) and the base excision repair (BER) pathways.…”

mentioning

confidence: 99%

Role of Dot1 in the Response to Alkylating DNA Damage in Saccharomyces cerevisiae: Regulation of DNA Damage Tolerance by the Error-Prone Polymerases Polζ/Rev1

Conde

San-Segundo

2008

Genetics

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Maintenance of genomic integrity relies on a proper response to DNA injuries integrated by the DNA damage checkpoint; histone modifications play an important role in this response. Dot1 methylates lysine 79 of histone H3. In Saccharomyces cerevisiae, Dot1 is required for the meiotic recombination checkpoint as well as for chromatin silencing and the G 1 /S and intra-S DNA damage checkpoints in vegetative cells. Here, we report the analysis of the function of Dot1 in the response to alkylating damage. Unexpectedly, deletion of DOT1 results in increased resistance to the alkylating agent methyl methanesulfonate (MMS). This phenotype is independent of the dot1 silencing defect and does not result from reduced levels of DNA damage. Deletion of DOT1 partially or totally suppresses the MMS sensitivity of various DNA repair mutants (rad52, rad54, yku80, rad1, rad14, apn1, rad5, rad30). However, the rev1 dot1 and rev3 dot1 mutants show enhanced MMS sensitivity and dot1 does not attenuate the MMS sensitivity of rad52 rev3 or rad52 rev1. In addition, Rev3-dependent MMS-induced mutagenesis is increased in dot1 cells. We propose that Dot1 inhibits translesion synthesis (TLS) by Polz/Rev1 and that the MMS resistance observed in the dot1 mutant results from the enhanced TLS activity.

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Damage-induced recombination in the yeast Saccharomyces cerevisiae

Cited by 54 publications

References 114 publications

Mutations of the Yku80 C Terminus and Xrs2 FHA Domain Specifically Block Yeast Nonhomologous End Joining

Mutations of the Yku80 C Terminus and Xrs2 FHA Domain Specifically Block Yeast Nonhomologous End Joining

Double-strand breaks associated with repetitive DNA can reshape the genome

Role of Dot1 in the Response to Alkylating DNA Damage in Saccharomyces cerevisiae: Regulation of DNA Damage Tolerance by the Error-Prone Polymerases Polζ/Rev1

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