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Mammalian CNTD1 is critical for meiotic crossover maturation and deselection of excess precrossover sites.

ABSTRACT: Meiotic crossovers (COs) are crucial for ensuring accurate homologous chromosome segregation during meiosis I. Because the double-strand breaks (DSBs) that initiate meiotic recombination greatly outnumber eventual COs, this process requires exquisite regulation to narrow down the pool of DSB intermediates that may form COs. In this paper, we identify a cyclin-related protein, CNTD1, as a critical mediator of this process. Disruption of Cntd1 results in failure to localize CO-specific factors MutL? and HEI10 at designated CO sites and also leads to prolonged high levels of pre-CO intermediates marked by MutS? and RNF212. These data show that maturation of COs is intimately coupled to deselection of excess pre-CO sites to yield a limited number of COs and that CNTD1 coordinates these processes by regulating the association between the RING finger proteins HEI10 and RNF212 and components of the CO machinery.

SUBMITTER: Holloway JK

PROVIDER: S-EPMC4050721 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Mammalian CNTD1 is critical for meiotic crossover maturation and deselection of excess precrossover sites.

Holloway J Kim JK Sun Xianfei X Yokoo Rayka R Villeneuve Anne M AM Cohen Paula E PE

The Journal of cell biology 20140602 5

Meiotic crossovers (COs) are crucial for ensuring accurate homologous chromosome segregation during meiosis I. Because the double-strand breaks (DSBs) that initiate meiotic recombination greatly outnumber eventual COs, this process requires exquisite regulation to narrow down the pool of DSB intermediates that may form COs. In this paper, we identify a cyclin-related protein, CNTD1, as a critical mediator of this process. Disruption of Cntd1 results in failure to localize CO-specific factors Mut ...[more]

PMID: 24891606

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