Meiotic chromosomes: it takes two to tango

Gs, Roeder

doi:10.1101/gad.11.20.2600

Cited by 783 publications

(694 citation statements)

References 231 publications

(270 reference statements)

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“…Spo11-mediated DSBs initiate meiotic homologous recombination and the repair of these breaks is required for chromosome synapsis in most organisms including mammals (Roeder, 1997;Zickler and Kleckner, 1999;Keeney, 2001;Villeneuve and Hillers, 2001). The appearance of the breaks in leptotene is accompanied by the phosphorylation of histone H2ax over megabasesize chromatin regions (Mahadevaiah et al, 2001).…”

Section: Aspermatogenesismentioning

confidence: 99%

Characterizing a rat Brca2 knockout model

et al. 2006

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Evidence exists that BRCA2 carriers may have an elevated risk of breast, ovarian, colon, prostate, and pancreatic cancer. In general, carriers are defined as individuals with protein truncating mutations within the BRCA2 gene. Many Brca2 knockout lines have been produced and characterized in the mouse. We previously produced a rat Brca2 knockout strain in which there is a nonsense mutation in exon 11 between BRC repeats 2 and 3, and a truncated protein is produced. Interestingly, while such a mutation in homozygous mice would lead to limited survival of approximately 3 months, the Brca2 À/À rats are 100% viable and the vast majority live to over 1 year of age. Brca2 À/À rats show a phenotype of growth inhibition and sterility in both sexes. Aspermatogenesis in the Brca2 À/À rats is due to a failure of homologous chromosome synapsis. Long-term phenotypes include underdeveloped mammary glands, cataract formation and lifespan shortening due to the development of tumors and cancers in multiple organs. The establishment of the rat Brca2 knockout model provides a means to study the role of Brca2 in increasing cancer susceptibility and inducing a novel ocular phenotype not previously associated with this gene.

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Section: Aspermatogenesismentioning

confidence: 99%

Characterizing a rat Brca2 knockout model

et al. 2006

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“…Because crossover recombination structures (chiasmata) help to stabilize paired homologous chromosomes on the metaphase plate of meiosis I (Roeder, 1997), achiasmatic mutants should suffer nondisjunction of homologous chromosomes in meiosis I. Fission yeast cells disomic for chromosome III are viable (Niwa and Yanagida, 1985). In diploids or pseudodiploids the ade6-M210 and ade6-M216 alleles exhibit intragenic complementation (which is quite rare), so heterozygous ade6-M210/ade6-M216 cells form colonies on medium lacking adenine (Gutz, 1971).…”

Section: The Rec12-g202e Mutants Suffer Mis-segregation Of Chromosomementioning

confidence: 99%

A DNA binding motif of meiotic recombinase Rec12 (Spo11) defined by essential glycine-202, and persistence of Rec12 protein after completion of recombination

DeWall¹,

Davidson²,

Sharif³

et al. 2005

Gene

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The Rec12 (Spo11) protein of the fission yeast Schizosaccharomyces pombe is a meiosis-specific ortholog of the catalytic subunit of type VI topoisomerases and is thought to catalyze doublestrand DNA breaks that initiate recombination. We tested the hypothesis that the rec12-117 allele affects the choice of pathways by which recombination is resolved. DNA sequence analysis revealed a single missense mutation in the coding region (rec12-G202E). The corresponding glycine-202 residue of Rec12 protein is strictly conserved in proteins of the Rec12/Spo11/Top6A family. It maps to the base of the DNA binding pocket in the crystal structure of the archaeal ortholog, Top6A. The rec12-G202E mutants lacked crossover and non-crossover recombination, demonstrating that rec12-G202E does not affect choice of resolution pathway. Like rec12-D15 null mutants, the rec12-G202E mutants suffered chromosome segregation errors in meiosis I. The Rec12-G202E protein was as stable as wild-type Rec12, demonstrating that glycine-202 is essential for a biochemical activity of Rec12 protein, rather than for its stability. These findings suggest that Rec12 facilitates binding of the meiotic recombinase to its substrate, DNA. Interestingly, the bulk of Rec12 protein persisted until the time of anaphase I, and a portion of Rec12 protein persisted until the time of anaphase II, after which it was undetectable. This suggests that Rec12 protein has additional meiotic functions after completion of recombination in prophase, as inferred previously from genetic studies.

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“…51 Two coupled processes, the formation and the processing of DSBs are involved in meiotic recombination. The SPO11 gene product is responsible for enzymatic DNA cleavage to create DSBs and Mre11 subsequently processes these through its intrinsic exonuclease activity.…”

Section: Genes Involved In Meiotic Dna Recombinationmentioning

confidence: 99%

“…Rad51, a member of the RecA-strand exchange protein family, catalyzes the invasion of the single-strand DNA overhangs generated by Mre11 into a recipient homologous double-strand DNA molecule, thereby initiating the formation of D loops and the later steps of meiotic recombination. 51,52 Mutations in Rad51 confer an enhanced sensitivity to DNA damaging agents in yeast, a reduction in mitotic recombination and impaired meiosis. Silencing of the gene via RNAi in C. elegans results in high levels of embryonic lethality and increased frequency of males, 44,53,54 phenotypes encountered commonly in meiotic mutants.…”

Section: Genes Involved In Meiotic Dna Recombinationmentioning

confidence: 99%

Death and more: DNA damage response pathways in the nematode C. elegans

2003

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Genotoxic stress is a threat to our cells' genome integrity. Failure to repair DNA lesions properly after the induction of cell proliferation arrest can lead to mutations or large-scale genomic instability. Because such changes may have tumorigenic potential, damaged cells are often eliminated via apoptosis. Loss of this apoptotic response is actually one of the hallmarks of cancer. Towards the effort to elucidate the DNA damage-induced signaling steps leading to these biological events, an easily accessible model system is required, where the acquired knowledge can reveal the mechanisms underlying more complex organisms. Accumulating evidence coming from studies in Caenorhabditis elegans point to its usefulness as such. In the worm's germline, DNA damage can induce both cell cycle arrest and apoptosis, two responses that are spatially separated. The latter is a tightly controlled process that is genetically indistinguishable from developmental programmed cell death. Upstream of the central death machinery, components of the DNA damage signaling cascade lie and act either as sensors of the lesion or as transducers of the initial signal detected. This review summarizes the findings of several studies that specify the elements of the DNA damage-induced responses, as components of the cell cycle control machinery, the repairing process or the apoptotic outcome. The validity of C. elegans as a tool to further dissect the complex signaling network of these responses and the high potential for it to reveal important links to cancer and other genetic abnormalities are addressed.

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Meiotic chromosomes: it takes two to tango

Cited by 783 publications

References 231 publications

Characterizing a rat Brca2 knockout model

Characterizing a rat Brca2 knockout model

A DNA binding motif of meiotic recombinase Rec12 (Spo11) defined by essential glycine-202, and persistence of Rec12 protein after completion of recombination

Death and more: DNA damage response pathways in the nematode C. elegans

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