Diversity and Determinants of Meiotic Recombination Landscapes

Zelkowski, Mateusz; Olson, Mischa; Wang, Minghui; Pawlowski, Wojtek

doi:10.1016/j.tig.2019.02.002

Cited by 78 publications

(103 citation statements)

References 89 publications

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“…Unlike in somatic cells, TDP2 loss in mice does not affect meiotic progression or fertility, suggesting that NHEJ is not used for repairing meiotic SPO11linked DSBs [14]. This is consistent with the idea that DSBs in meiotic prophase are designated to be repaired by HR to promote obligate crossover between homologous chromosomes [20,21]. Studies in multiple organisms have demonstrated that MRN/MRX complex-dependent removal of SPO11-oligonucleotide from DSB sites is required for meiotic DSB repair.…”

Section: Introductionsupporting

confidence: 70%

NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis

Zhang

Tang

et al. 2020

Cell Death Differ

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DNA double-strand breaks (DSBs) pose a serious threat to genomic stability. Paradoxically, hundreds of programed DSBs are generated by SPO11 in meiotic prophase, which are exclusively repaired by homologous recombination (HR) to promote obligate crossover between homologous chromosomes. In somatic cells, MRE11-RAD50-NBS1 (MRN) complex-dependent DNA end resection is a prerequisite for HR repair, especially for DSBs that are covalently linked with proteins or chemicals. Interestingly, all meiotic DSBs are linked with SPO11 after being generated. Although MRN complex's function in meiotic DSB repair has been established in lower organisms, the role of MRN complex in mammalian meiotic DSB repair is not clear. Here, we show that MRN complex is essential for repairing meiotic SPO11-linked DSBs in male mice. In male germ cells, conditional inactivation of NBS1, a key component of MRN complex, causes dramatic reduction of DNA end resection and defective HR repair in meiotic prophase. NBS1 loss severely disrupts chromosome synapsis, generates abnormal chromosome structures, and eventually leads to meiotic arrest and male infertility in mice. Unlike in somatic cells, the recruitment of NBS1 to SPO11-linked DSB sites is MDC1-independent but requires other phosphorylated proteins. Collectively, our study not only reveals the significance of MRN complex in repairing meiotic DSBs but also discovers a unique mechanism that recruits MRN complex to SPO11-linked DSB sites.

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Section: Introductionsupporting

confidence: 70%

NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis

Zhang

Tang

et al. 2020

Cell Death Differ

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“…However, the mechanism by which each chromosome senses, recognizes, approaches, and interacts with its matching mate or homologue is a long-standing question. Recombination-dependent [24,25,26,27] and recombination-independent [28,29,30,31] mechanisms are known to participate in the homolog pairing. The difference between the two is whether the pairing requires programmed DNA double strand breaks (DSBs).…”

Section: Mg2+ Induces Dna Self-assembly and Nucleosome Self-assemblymentioning

confidence: 99%

New Aspects of Magnesium Function: A Key Regulator in Nucleosome Self-Assembly, Chromatin Folding and Phase Separation

Ohyama

2019

IJMS

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Metal cations are associated with many biological processes. The effects of these cations on nucleic acids and chromatin were extensively studied in the early stages of nucleic acid and chromatin research. The results revealed that some monovalent and divalent metal cations, including Mg2+, profoundly affect the conformations and stabilities of nucleic acids, the folding of chromatin fibers, and the extent of chromosome condensation. Apart from these effects, there have only been a few reports on the functions of these cations. In 2007 and 2013, however, Mg2+-implicated novel phenomena were found: Mg2+ facilitates or enables both self-assembly of identical double-stranded (ds) DNA molecules and self-assembly of identical nucleosomes in vitro. These phenomena may be deeply implicated in the heterochromatin domain formation and chromatin-based phase separation. Furthermore, a recent study showed that elevation of the intranuclear Mg2+ concentration causes unusual differentiation of mouse ES (embryonic stem) cells. All of these phenomena seem to be closely related to one another. Mg2+ seems to be a key regulator of chromatin dynamics and chromatin-based biological processes.

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“…Whilst recombination has previously been harnessed to great effect, its utility is limited in important staple food crops such as wheat (Saintenac et al, 2009;Choulet et al, 2014), maize (He et al, 2017), and barley (Higgins et al, 2014). The distribution of recombination events in these crops is strongly skewed toward the distal ends of the chromosomes, with little to no crossovers (COs) occurring in the region surrounding the centromere, known as the pericentromeric region (Zelkowski et al, 2019). This contrasts with Arabidopsis, in which the distribution of COs is much more uniform, with only the centromeric region showing highly reduced numbers of COs (Giraut et al, 2011;Choi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Examining the Effects of Temperature on Recombination in Wheat

2020

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Meiotic recombination plays a crucial role in the generation of new varieties. The effectiveness of recombination is limited by the distribution of crossover events, which in wheat and many other crops is skewed toward the distal regions of the chromosomes. Whole-genome sequencing of wheat has revealed that there are numerous important genes in the pericentromeric regions, which are inaccessible to manipulation due to the lack of crossover events. Studies in barley have shown that the distribution of recombination events can be shifted toward the centromeres by increasing temperature during meiosis. Here we present an analysis of the effects of temperature on the distribution and frequency of recombination events in wheat. Our data show that although increased temperature during meiosis does cause an inward shift in recombination distribution for some chromosomes, its overall utility is limited, with many genes remaining highly linked.

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Diversity and Determinants of Meiotic Recombination Landscapes

Cited by 78 publications

References 89 publications

NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis

NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis

New Aspects of Magnesium Function: A Key Regulator in Nucleosome Self-Assembly, Chromatin Folding and Phase Separation

Examining the Effects of Temperature on Recombination in Wheat

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