Meiotic double strand breaks repair in sexually reproducing eukaryotes: We are not all equal

Volpe, Adriana La; Barchi, Marco

doi:10.1016/j.yexcr.2012.03.014

Cited by 18 publications

(13 citation statements)

References 63 publications

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“…The morphology and number of diakinesis chromosomes can serve as a readout of meiotic recombination defects [58]. During diakinesis, homologous chromosomes pair and restructure forming bivalents.…”

Section: Resultsmentioning

confidence: 99%

Combinatorial Regulation of Meiotic Holliday Junction Resolution in C. elegans by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases

et al. 2013

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Holliday junctions (HJs) are cruciform DNA structures that are created during recombination events. It is a matter of considerable importance to determine the resolvase(s) that promote resolution of these structures. We previously reported that C. elegans GEN-1 is a symmetrically cleaving HJ resolving enzyme required for recombinational repair, but we could not find an overt role in meiotic recombination. Here we identify C. elegans proteins involved in resolving meiotic HJs. We found no evidence for a redundant meiotic function of GEN-1. In contrast, we discovered two redundant HJ resolution pathways likely coordinated by the SLX-4 scaffold protein and also involving the HIM-6/BLM helicase. SLX-4 associates with the SLX-1, MUS-81 and XPF-1 nucleases and has been implicated in meiotic recombination in C. elegans. We found that C. elegans [mus-81; xpf-1], [slx-1; xpf-1], [mus-81; him-6] and [slx-1; him-6] double mutants showed a similar reduction in survival rates as slx-4. Analysis of meiotic diakinesis chromosomes revealed a distinct phenotype in these double mutants. Instead of wild-type bivalent chromosomes, pairs of “univalents” linked by chromatin bridges occur. These linkages depend on the conserved meiosis-specific transesterase SPO-11 and can be restored by ionizing radiation, suggesting that they represent unresolved meiotic HJs. This suggests the existence of two major resolvase activities, one provided by XPF-1 and HIM-6, the other by SLX-1 and MUS-81. In all double mutants crossover (CO) recombination is reduced but not abolished, indicative of further redundancy in meiotic HJ resolution. Real time imaging revealed extensive chromatin bridges during the first meiotic division that appear to be eventually resolved in meiosis II, suggesting back-up resolution activities acting at or after anaphase I. We also show that in HJ resolution mutants, the restructuring of chromosome arms distal and proximal to the CO still occurs, suggesting that CO initiation but not resolution is likely to be required for this process.

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Section: Resultsmentioning

confidence: 99%

Combinatorial Regulation of Meiotic Holliday Junction Resolution in C. elegans by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases

et al. 2013

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“…While meiosis recombination is a conserved process in eukaryotes, there are clear differences among organisms [52]. Interestingly, yeast, plants and C. elegans do not have a Meiob homolog (Figure 1A).…”

Section: Discussionmentioning

confidence: 99%

MEIOB Targets Single-Strand DNA and Is Necessary for Meiotic Recombination

et al. 2013

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Meiotic recombination is a mandatory process for sexual reproduction. We identified a protein specifically implicated in meiotic homologous recombination that we named: meiosis specific with OB domain (MEIOB). This protein is conserved among metazoan species and contains single-strand DNA binding sites similar to those of RPA1. Our studies in vitro revealed that both recombinant and endogenous MEIOB can be retained on single-strand DNA. Those in vivo demonstrated the specific expression of Meiob in early meiotic germ cells and the co-localization of MEIOB protein with RPA on chromosome axes. MEIOB localization in Dmc1 −/− spermatocytes indicated that it accumulates on resected DNA. Homologous Meiob deletion in mice caused infertility in both sexes, due to a meiotic arrest at a zygotene/pachytene-like stage. DNA double strand break repair and homologous chromosome synapsis were impaired in Meiob −/− meiocytes. Interestingly MEIOB appeared to be dispensable for the initial loading of recombinases but was required to maintain a proper number of RAD51 and DMC1 foci beyond the zygotene stage. In light of these findings, we propose that RPA and this new single-strand DNA binding protein MEIOB, are essential to ensure the proper stabilization of recombinases which is required for successful homology search and meiotic recombination.

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“…TEX11 promotes the initiation and/or maintenance of crossover formation in a distinct way ( Figure 1). Meiotic homologous recombination is initiated by the formation of DSBs, depending on several accessory factors [La Volpe and Barchi 2012]. Testis expressed gene 15 (TEX15) regulates the loading of DNA repair proteins onto sites of DSBs [Inagaki et al 2010].…”

Section: Introductionmentioning

confidence: 99%

Six polymorphisms in genes involved in DNA double-strand break repair and chromosome synapsis: association with male infertility

Zhang

Min²,

Ding³

et al. 2015

Systems Biology in Reproductive Medicine

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Four genes involved in DNA double-strand break repair and chromosome synapsis, i.e., testis expressed gene 11 (TEX11), testis expressed gene 15 (TEX15), mutL homolog 1 (MLH1), and homolog 3 (MLH3), play critical roles in genome integrity, meiotic recombination, and gametogenesis. We explored the possible association between single nucleotide polymorphisms (SNPs) in these genes and idiopathic male infertility involving azoospermia or oligozoospermia. A total of 614 fertile control and infertile men were recruited to this study in Sichuan, China. The latter group included 244 men with azoospermia and 72 men with oligozoospermia. Six SNPs in the TEX11, TEX15, MLH1, and MLH3 genes were investigated in both patients and controls by sequencing. The frequency distributions of SNPs rs6525433, rs175080, rs6525433-rs4844247, and rs1800734-rs175080 were found to be significantly different between patients and control groups (p < 0.05), while rs4844247, rs323344, rs323346, and rs1800734 showed no significant difference between the two cohorts. Thus, the SNPs TEX11 rs6525433, MLH3 rs175080, rs6525433-rs4844247, and rs1800734-rs175080 might be associated with male infertility.

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Meiotic double strand breaks repair in sexually reproducing eukaryotes: We are not all equal

Cited by 18 publications

References 63 publications

Combinatorial Regulation of Meiotic Holliday Junction Resolution in C. elegans by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases

Combinatorial Regulation of Meiotic Holliday Junction Resolution in C. elegans by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases

MEIOB Targets Single-Strand DNA and Is Necessary for Meiotic Recombination

Six polymorphisms in genes involved in DNA double-strand break repair and chromosome synapsis: association with male infertility

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