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Rad51-independent interchromosomal double-strand break repair by gene conversion requires Rad52 but not Rad55, Rad57, or Dmc1.
Mol Cell Biol. 2008 Feb; 28(3):897-906.MC

Abstract

Homologous recombination (HR) is critical for DNA double-strand break (DSB) repair and genome stabilization. In yeast, HR is catalyzed by the Rad51 strand transferase and its "mediators," including the Rad52 single-strand DNA-annealing protein, two Rad51 paralogs (Rad55 and Rad57), and Rad54. A Rad51 homolog, Dmc1, is important for meiotic HR. In wild-type cells, most DSB repair results in gene conversion, a conservative HR outcome. Because Rad51 plays a central role in the homology search and strand invasion steps, DSBs either are not repaired or are repaired by nonconservative single-strand annealing or break-induced replication mechanisms in rad51Delta mutants. Although DSB repair by gene conversion in the absence of Rad51 has been reported for ectopic HR events (e.g., inverted repeats or between plasmids), Rad51 has been thought to be essential for DSB repair by conservative interchromosomal (allelic) gene conversion. Here, we demonstrate that DSBs stimulate gene conversion between homologous chromosomes (allelic conversion) by >30-fold in a rad51Delta mutant. We show that Rad51-independent allelic conversion and break-induced replication occur independently of Rad55, Rad57, and Dmc1 but require Rad52. Unlike DSB-induced events, spontaneous allelic conversion was detected in both rad51Delta and rad52Delta mutants, but not in a rad51Delta rad52Delta double mutant. The frequencies of crossovers associated with DSB-induced gene conversion were similar in the wild type and the rad51Delta mutant, but discontinuous conversion tracts were fivefold more frequent and tract lengths were more widely distributed in the rad51Delta mutant, indicating that heteroduplex DNA has an altered structure, or is processed differently, in the absence of Rad51.

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Authors+Show Affiliations

Pohl TJ
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Nickoloff JA
No affiliation info available

MeSH

Adenosine TriphosphatasesCell Cycle ProteinsDNA Breaks, Double-StrandedDNA RepairDNA Repair EnzymesDNA-Binding ProteinsGene ConversionNucleic Acid ConformationNucleic Acid HeteroduplexesRad51 RecombinaseRad52 DNA Repair and Recombination ProteinSaccharomyces cerevisiaeSaccharomyces cerevisiae Proteins

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18039855

Citation

Pohl, Thomas J., and Jac A. Nickoloff. "Rad51-independent Interchromosomal Double-strand Break Repair By Gene Conversion Requires Rad52 but Not Rad55, Rad57, or Dmc1." Molecular and Cellular Biology, vol. 28, no. 3, 2008, pp. 897-906.
Pohl TJ, Nickoloff JA. Rad51-independent interchromosomal double-strand break repair by gene conversion requires Rad52 but not Rad55, Rad57, or Dmc1. Mol Cell Biol. 2008;28(3):897-906.
Pohl, T. J., & Nickoloff, J. A. (2008). Rad51-independent interchromosomal double-strand break repair by gene conversion requires Rad52 but not Rad55, Rad57, or Dmc1. Molecular and Cellular Biology, 28(3), 897-906.
Pohl TJ, Nickoloff JA. Rad51-independent Interchromosomal Double-strand Break Repair By Gene Conversion Requires Rad52 but Not Rad55, Rad57, or Dmc1. Mol Cell Biol. 2008;28(3):897-906. PubMed PMID: 18039855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rad51-independent interchromosomal double-strand break repair by gene conversion requires Rad52 but not Rad55, Rad57, or Dmc1. AU - Pohl,Thomas J, AU - Nickoloff,Jac A, Y1 - 2007/11/26/ PY - 2007/11/28/pubmed PY - 2008/3/18/medline PY - 2007/11/28/entrez SP - 897 EP - 906 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 28 IS - 3 N2 - Homologous recombination (HR) is critical for DNA double-strand break (DSB) repair and genome stabilization. In yeast, HR is catalyzed by the Rad51 strand transferase and its "mediators," including the Rad52 single-strand DNA-annealing protein, two Rad51 paralogs (Rad55 and Rad57), and Rad54. A Rad51 homolog, Dmc1, is important for meiotic HR. In wild-type cells, most DSB repair results in gene conversion, a conservative HR outcome. Because Rad51 plays a central role in the homology search and strand invasion steps, DSBs either are not repaired or are repaired by nonconservative single-strand annealing or break-induced replication mechanisms in rad51Delta mutants. Although DSB repair by gene conversion in the absence of Rad51 has been reported for ectopic HR events (e.g., inverted repeats or between plasmids), Rad51 has been thought to be essential for DSB repair by conservative interchromosomal (allelic) gene conversion. Here, we demonstrate that DSBs stimulate gene conversion between homologous chromosomes (allelic conversion) by >30-fold in a rad51Delta mutant. We show that Rad51-independent allelic conversion and break-induced replication occur independently of Rad55, Rad57, and Dmc1 but require Rad52. Unlike DSB-induced events, spontaneous allelic conversion was detected in both rad51Delta and rad52Delta mutants, but not in a rad51Delta rad52Delta double mutant. The frequencies of crossovers associated with DSB-induced gene conversion were similar in the wild type and the rad51Delta mutant, but discontinuous conversion tracts were fivefold more frequent and tract lengths were more widely distributed in the rad51Delta mutant, indicating that heteroduplex DNA has an altered structure, or is processed differently, in the absence of Rad51. SN - 1098-5549 UR - https://www.unboundmedicine.com/medline/citation/18039855/Rad51_independent_interchromosomal_double_strand_break_repair_by_gene_conversion_requires_Rad52_but_not_Rad55_Rad57_or_Dmc1_ DB - PRIME DP - Unbound Medicine ER -