Publication Date:
2010-03-30
Description:
Repair of DNA double-strand breaks (DSBs) by homologous recombination is crucial for cell proliferation and tumour suppression. However, despite its importance, the molecular intermediates of mitotic DSB repair remain undefined. The double Holliday junction (DHJ), presupposed to be the central intermediate for more than 25 years, has only been identified during meiotic recombination. Moreover, evidence has accumulated for alternative, DHJ-independent mechanisms, raising the possibility that DHJs are not formed during DSB repair in mitotically cycling cells. Here we identify intermediates of DSB repair by using a budding-yeast assay system designed to mimic physiological DSB repair. This system uses diploid cells and provides the possibility for allelic recombination either between sister chromatids or between homologues, as well as direct comparison with meiotic recombination at the same locus. In mitotically cycling cells, we detect inter-homologue joint molecule (JM) intermediates whose strand composition and size are identical to those of the canonical DHJ structures observed in meiosis. However, in contrast to meiosis, JMs between sister chromatids form in preference to those between homologues. Moreover, JMs seem to represent a minor pathway of DSB repair in mitotic cells, being detected at about tenfold lower levels (per DSB) than during meiotic recombination. Thus, although DHJs are identified as intermediates of DSB-promoted recombination in both mitotic and meiotic cells, their formation is distinctly regulated according to the specific dictates of the two cellular programs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851831/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851831/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bzymek, Malgorzata -- Thayer, Nathaniel H -- Oh, Steve D -- Kleckner, Nancy -- Hunter, Neil -- GM025326/GM/NIGMS NIH HHS/ -- GM074223/GM/NIGMS NIH HHS/ -- R01 GM025326/GM/NIGMS NIH HHS/ -- R01 GM025326-31/GM/NIGMS NIH HHS/ -- R01 GM074223/GM/NIGMS NIH HHS/ -- R01 GM074223-05/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Apr 8;464(7290):937-41. doi: 10.1038/nature08868. Epub 2010 Mar 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of California Davis, Davis, California 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20348905" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Chromatids/genetics/metabolism
;
Crossing Over, Genetic/genetics
;
*DNA Breaks, Double-Stranded
;
*DNA Repair
;
DNA, Cruciform/genetics/*metabolism
;
Diploidy
;
Meiosis/genetics
;
Mitosis/genetics
;
Models, Genetic
;
RecQ Helicases/genetics/metabolism
;
Saccharomyces cerevisiae/cytology/*genetics
;
Saccharomyces cerevisiae Proteins/genetics/metabolism
;
Sister Chromatid Exchange/genetics
;
Time Factors
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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