Alternative induction of meiotic recombination from single-base lesions of DNA deaminases.
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.
Pauklin
Siim
S
INSERM U783, Faculté de Médicine Necker-Enfants Malades, 75730 Paris Cedex 15, France.
Burkert
Julia S
JS
Martin
Julie
J
Osman
Fekret
F
Weller
Sandra
S
Boulton
Simon J
SJ
Whitby
Matthew C
MC
Petersen-Mahrt
Svend K
SK
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D003564:Cytidine Deaminase / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008540:Meiosis / Q000502:physiology*; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000099257:Meiotic Recombination Protein SPO11
D029742:Caenorhabditis elegans Proteins; D003564:Cytidine Deaminase; D004706:Endodeoxyribonucleases; D004950:Esterases; D051135:Rad51 Recombinase; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000099257:Meiotic Recombination Protein SPO11