A novel plant gene essential for meiosis is related to the human CtIP and the yeast COM1/SAE2 gene.
Obligatory homologous recombination (HR) is required for chiasma formation and chromosome segregation in meiosis I. Meiotic HR is initiated by DNA double-strand breaks (DSBs), generated by Spo11, a homologue of the archaebacterial topoisomerase subunit Top6A. In Saccharomyces cerevisiae, Rad50, Mre11 and Com1/Sae2 are essential to process an intermediate of the cleavage reaction consisting of Spo11 covalently linked to the 5' termini of DNA. While Rad50 and Mre11 also confer genome stability to vegetative cells and are well conserved in evolution, Com1/Sae2 was believed to be fungal-specific. Here, we identify COM1/SAE2 homologues in all eukaryotic kingdoms. Arabidopsis thaliana Com1/Sae2 mutants are sterile, accumulate AtSPO11-1 during meiotic prophase and fail to form AtRAd51 foci despite the presence of unrepaired DSBs. Furthermore, DNA fragmentation in AtCom1 is suppressed by eliminating AtSPO11-1. In addition, AtCOM1 is specifically required for mitomycin C resistance. Interestingly, we identified CtIP, an essential protein interacting with the DNA repair machinery, as the mammalian homologue of Com1/Sae2, with important implications for the molecular role of CtIP.
Uanschou
Clemens
C
Department of Chromosome Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria.
Siwiec
Tanja
T
Pedrosa-Harand
Andrea
A
Kerzendorfer
Claudia
C
Sanchez-Moran
Eugenio
E
Novatchkova
Maria
M
Akimcheva
Svetlana
S
Woglar
Alexander
A
Klein
Franz
F
Schlögelhofer
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D053938:DNA Fragmentation; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D017343:Genes, Plant; D006801:Humans; D008540:Meiosis / Q000502:physiology*; D016685:Mitomycin / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000378:metabolism; D010641:Phenotype; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D000099257:Meiotic Recombination Protein SPO11
D029681:Arabidopsis Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D016685:Mitomycin; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D029701:Saccharomyces cerevisiae Proteins; C414986:AtGR1 protein, Arabidopsis; C513033:DMC1 protein, S cerevisiae; C107849:SAE2 protein, S cerevisiae; C477460:Spo11-1 protein, Arabidopsis; D000099257:Meiotic Recombination Protein SPO11; C427727:rad50 protein, Arabidopsis; C410741:RBBP8 protein, human