An MCM family protein promotes interhomolog recombination by preventing precocious intersister repair of meiotic DSBs

Autoři: Miao Tian aff001;  Josef Loidl aff001
Působiště autorů: Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria aff001
Vyšlo v časopise: An MCM family protein promotes interhomolog recombination by preventing precocious intersister repair of meiotic DSBs. PLoS Genet 15(12): e32767. doi:10.1371/journal.pgen.1008514
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008514


Recombinational repair of meiotic DNA double-strand breaks (DSBs) uses the homologous chromosome as a template, although the sister chromatid offers itself as a spatially more convenient substrate. In many organisms, this choice is reinforced by the recombination protein Dmc1. In Tetrahymena, the repair of DSBs, which are formed early in prophase, is postponed to late prophase when homologous chromosomes and sister chromatids become juxtaposed owing to tight parallel packing in the thread-shaped nucleus, and thus become equally suitable for use as repair templates. The delay in DSB repair is achieved by rejection of the invading strand by the Sgs1 helicase in early meiotic prophase. In the absence of Mcmd1, a meiosis-specific minichromosome maintenance (MCM)-like protein (and its partner Pamd1), Dmc1 is prematurely lost from chromatin and DNA synthesis (as monitored by BrdU incorporation) takes place in early prophase. In mcmd1Δ and pamd1Δ mutants, only a few crossovers are formed. In a mcmd1Δ hop2Δ double mutant, normal timing of Dmc1 loss and DNA synthesis is restored. Because Tetrahymena Hop2 is believed to enable homologous strand invasion, we conclude that Dmc1 loss in the absence of Mcmd1 affects only post-invasion recombination intermediates. Therefore, we propose that the Dmc1 nucleofilament becomes dismantled immediately after forming a heteroduplex with a template strand. As a consequence, repair synthesis and D-loop extension starts in early prophase intermediates and prevents strand rejection before the completion of homologous pairing. In this case, DSB repair may primarily use the sister chromatid. We conclude that Mcmd1‒Pamd1 protects the Dmc1 nucleofilament from premature dismantling, thereby suppressing precocious repair synthesis and excessive intersister strand exchange at the cost of homologous recombination.

Klíčová slova:

DNA recombination – DNA repair – DNA synthesis – Homologous recombination – Meiosis – Meiotic prophase – Recombinant proteins – Tetrahymena


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