The mouse Spo11 gene is required for meiotic chromosome synapsis.
The Spo11 protein initiates meiotic recombination by generating DNA double-strand breaks (DSBs) and is required for meiotic synapsis in S. cerevisiae. Surprisingly, Spo11 homologs are dispensable for synapsis in C. elegans and Drosophila yet required for meiotic recombination. Disruption of mouse Spo11 results in infertility. Spermatocytes arrest prior to pachytene with little or no synapsis and undergo apoptosis. We did not detect Rad51/Dmc1 foci in meiotic chromosome spreads, indicating DSBs are not formed. Cisplatin-induced DSBs restored Rad51/Dmc1 foci and promoted synapsis. Spo11 localizes to discrete foci during leptotene and to homologously synapsed chromosomes. Other mouse mutants that arrest during meiotic prophase (Atm -/-, Dmc1 -/-, mei1, and Morc(-/-)) showed altered Spo11 protein localization and expression. We speculate that there is an additional role for Spo11, after it generates DSBs, in synapsis.
Romanienko
P J
PJ
Genetics and Biochemistry Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health 20892, Bethesda, MD, USA.
Camerini-Otero
R D
RD
D000251:Adenosine Triphosphatases / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins; D023902:Chromosome Pairing / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D007247:Infertility, Female / Q000235:genetics / Q000473:pathology; D007248:Infertility, Male / Q000235:genetics / Q000473:pathology; D008297:Male; D008540:Meiosis / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D010053:Ovary / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport; D011506:Proteins; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051135:Rad51 Recombinase; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D013090:Spermatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000378:metabolism / Q000473:pathology; D000099257:Meiotic Recombination Protein SPO11
D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002945:Cisplatin; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D004950:Esterases; D011506:Proteins; D012333:RNA, Messenger; D051135:Rad51 Recombinase; D029701:Saccharomyces cerevisiae Proteins; D000099257:Meiotic Recombination Protein SPO11; C495151:RAD51 protein, S cerevisiae; C495154:Rad51 protein, mouse