Document Detail

Alternative induction of meiotic recombination from single-base lesions of DNA deaminases.
MedLine Citation:
PMID:  19237686     Owner:  NLM     Status:  MEDLINE    
Meiotic recombination enhances genetic diversity as well as ensures proper segregation of homologous chromosomes, requiring Spo11-initiated double-strand breaks (DSBs). DNA deaminases act on regions of single-stranded DNA and deaminate cytosine to uracil (dU). In the immunoglobulin locus, this lesion will initiate point mutations, gene conversion, and DNA recombination. To begin to delineate the effect of induced base lesions on meiosis, we analyzed the effect of expressing DNA deaminases (activation-induced deaminase, AID, and APOBEC3C) in germ cells. We show that meiotic dU:dG lesions can partially rescue a spo11Delta phenotype in yeast and worm. In rec12 Schizosaccharomyces pombe, AID expression increased proper chromosome segregation, thereby enhancing spore viability, and induced low-frequency meiotic crossovers. Expression of AID in the germ cells of Caenorhabditis elegans spo-11 induced meiotic RAD-51 foci formation and chromosomal bivalency and segregation, as well as an increase in viability. RNAi experiments showed that this rescue was dependent on uracil DNA-glycosylase (Ung). Furthermore, unlike ionizing radiation-induced spo-11 rescue, AID expression did not induce large numbers of DSBs during the rescue. This suggests that the products of DNA deamination and base excision repair, such as uracil, an abasic site, or a single-stranded nick, are sufficient to initiate and alter meiotic recombination in uni- and multicellular organisms.
Siim Pauklin; Julia S Burkert; Julie Martin; Fekret Osman; Sandra Weller; Simon J Boulton; Matthew C Whitby; Svend K Petersen-Mahrt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-23
Journal Detail:
Title:  Genetics     Volume:  182     ISSN:  0016-6731     ISO Abbreviation:  Genetics     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-30     Completed Date:  2009-07-31     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  0374636     Medline TA:  Genetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  41-54     Citation Subset:  IM    
INSERM U783, Faculté de Médicine Necker-Enfants Malades, 75730 Paris Cedex 15, France.
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MeSH Terms
Animals, Genetically Modified
Caenorhabditis elegans / genetics,  metabolism
Caenorhabditis elegans Proteins / genetics,  metabolism
Chromosome Segregation*
Cytidine Deaminase / genetics*
DNA Breaks, Double-Stranded
DNA Repair
Esterases / genetics,  metabolism
In Situ Nick-End Labeling
Meiosis / physiology*
Rad51 Recombinase / genetics,  metabolism
Recombination, Genetic*
Saccharomyces cerevisiae / genetics,  metabolism
Saccharomyces cerevisiae Proteins / genetics,  metabolism
Schizosaccharomyces / genetics,  metabolism
Schizosaccharomyces pombe Proteins / genetics,  metabolism
Grant Support
//Cancer Research UK
Reg. No./Substance:
0/Caenorhabditis elegans Proteins; 0/Saccharomyces cerevisiae Proteins; 0/Schizosaccharomyces pombe Proteins; 0/Spo11 protein; EC 2.7.7.-/Rad51 Recombinase; EC 3.1.-/Esterases; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC Deaminase

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