Meiotic Recombination in C. elegans Initiates by a Conserved Mechanism and Is Dispensable for Homologous Chromosome Synapsis

Dernburg, Abby F.; McDonald, Kent L.; Moulder, Gary; Barstead, Robert; Dresser, Michael E.; Villeneuve, Anne M.

doi:10.1016/s0092-8674(00)81481-6

Cited by 727 publications

(831 citation statements)

References 48 publications

(10 reference statements)

Supporting

Mentioning

799

Contrasting

Unclassified

Order By: Relevance

“…Although this structural similarity is consistent with a role for SPO11 as the enzyme that catalyzes meiosis-speci¢c DSBs, enzymatic activity for yeast or other eukaryotic SPO11 proteins has not been demonstrated. Sequence homology with the SPO11 gene product and similar function in meiosis has been noted in rec12 of ¢ssion yeast [8], £y MEI-W68 [9] and worm Spo-11 [10], indicating that the underlying mechanism of meiotic recombination is likely to be highly conserved among eukaryotes. However, unlike the situation for budding yeast, chromosome synapsis is not impaired in the mei-W68 and spo-11 mutants.…”

Section: Introductionmentioning

confidence: 80%

Differential gene expression of mammalian SPO11/TOP6A homologs during meiosis¹

et al. 1999

View full text Add to dashboard Cite

As the initiator of DNA double-strand breaks during meiosis in Saccharomyces cerevisiae, the SPO11 protein is essential for recombination. Similarity between SPO11 and archaebacterial TOP6A proteins points to evolutionary specialization of a DNA cleavage function for meiotic recombination. To determine whether this extends to mammals, we isolated and characterized mouse and human SPO11 cDNAs. Mammalian SPO11 genes were found to be expressed at high levels only in testis, wherein mouse Spo11 transcript is restricted primarily to meiotic germ cells and is maximally expressed at midpachynema. Mouse Spo11 is located near the distal end of chromosome 2, while human SPO11 is found in the homologous position of chromosome 20q13.2^13.3, a region that is amplified in some breast cancers. Sequence homology and differential expression together support a highly conserved role for SPO11 in the enzymatic cleavage of DNA that accompanies meiotic recombination.z 1999 Federation of European Biochemical Societies.

show abstract

Section: Introductionmentioning

confidence: 80%

Differential gene expression of mammalian SPO11/TOP6A homologs during meiosis¹

et al. 1999

View full text Add to dashboard Cite

show abstract

“…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. Moreover, a dramatic increase in germ cell apoptosis is observed when rad-51 is inactivated.…”

Section: Genes Involved In Meiotic Dna Recombinationmentioning

confidence: 99%

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

2003

View full text Add to dashboard Cite

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.

show abstract

“…While in most organisms homologous chromosome pairing and synapsis is dependent on the appearances of such DSBs, it is not so in C. elegans in which homologue recognition and pairing is accomplished by means of specialized genomic sequences and proteins [1]. In this organism, in absence of spo-11, although meiotic recombination does not occur and homologous chromosomes appear as univalents by the end of meiotic prophase and fail to properly segregate, meiotic synapsis takes place and meiosis proceeds [2]. Interestingly, in the meiotic mutant cra-1, unlike in the wild type, DSB formation is required to promote the polymerization of the central region Recombination is initiated by SPO11-generated double strand breaks (DSBs) formation (a).…”

Section: Recombination Initiationmentioning

confidence: 99%