Dataset Information

Network Rewiring of Homologous Recombination Enzymes during Mitotic Proliferation and Meiosis.

ABSTRACT: Homologous recombination (HR) is essential for high-fidelity DNA repair during mitotic proliferation and meiosis. Yet, context-specific modifications must tailor the recombination machinery to avoid (mitosis) or enforce (meiosis) the formation of reciprocal exchanges-crossovers-between recombining chromosomes. To obtain molecular insight into how crossover control is achieved, we affinity purified 7 DNA-processing enzymes that channel HR intermediates into crossovers or noncrossovers from vegetative cells or cells undergoing meiosis. Using mass spectrometry, we provide a global characterization of their composition and reveal mitosis- and meiosis-specific modules in the interaction networks. Functional analyses of meiosis-specific interactors of MutL?-Exo1 identified Rtk1, Caf120, and Chd1 as regulators of crossing-over. Chd1, which transiently associates with Exo1 at the prophase-to-metaphase I transition, enables the formation of MutL?-dependent crossovers through its conserved ability to bind and displace nucleosomes. Thus, rewiring of the HR network, coupled to chromatin remodeling, promotes context-specific control of the recombination outcome.

SUBMITTER: Wild P

PROVIDER: S-EPMC6715774 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Network Rewiring of Homologous Recombination Enzymes during Mitotic Proliferation and Meiosis.

Wild Philipp P Susperregui Aitor A Piazza Ilaria I Dörig Christian C Oke Ashwini A Arter Meret M Yamaguchi Miyuki M Hilditch Alexander T AT Vuina Karla K Chan Ki Choi KC Gromova Tatiana T Haber James E JE Fung Jennifer C JC Picotti Paola P Matos Joao J

Molecular cell 20190724 4

Homologous recombination (HR) is essential for high-fidelity DNA repair during mitotic proliferation and meiosis. Yet, context-specific modifications must tailor the recombination machinery to avoid (mitosis) or enforce (meiosis) the formation of reciprocal exchanges-crossovers-between recombining chromosomes. To obtain molecular insight into how crossover control is achieved, we affinity purified 7 DNA-processing enzymes that channel HR intermediates into crossovers or noncrossovers from vegeta ...[more]

PMID: 31351878

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Project description:The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC-dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC-dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post-SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1?/? implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function.

Project description:IntroductionMeiotic recombination (or crossover, CO) is essential for gamete fertility as well as for alleles and genes reshuffling that is at the heart of plant breeding. However, CO remains a limited event, which strongly hampers the rapid production of original and improved cultivars. RecQ4 is a gene encoding a helicase protein that, when mutated, contributes to improve recombination rate in all species where it has been evaluated so far.MethodsIn this study, we developed wheat (Triticum aestivum L.) triple mutant (TM) for the three homoeologous copies of TaRecQ4 as well as mutants for two copies and heterozygous for the last one (Htz-A, Htz-B, Htz-D).ResultsPhenotypic observation revealed a significant reduction of fertility and pollen viability in TM and Htz-B plants compared to wild type plants suggesting major defects during meiosis. Cytogenetic analyses of these plants showed that complete absence of TaRecQ4 as observed in TM plants, leads to chromosome fragmentation during the pachytene stage, resulting in problems in the segregation of chromosomes during meiosis. Htz-A and Htz-D mutants had an almost normal meiotic progression indicating that both TaRecQ4-A and TaRecQ4-D copies are functional and that there is no dosage effect for TaRecQ4 in bread wheat. On the contrary, the TaRecQ4-B copy seems knocked-out, probably because of a SNP leading to a Threonine>Alanine change at position 539 (T539A) of the protein, that occurs in the crucial helicase ATP bind/DEAD/ResIII domain which unwinds nucleic acids. Occurrence of numerous multivalents in TM plants suggests that TaRecQ4 could also play a role in the control of homoeologous recombination.DiscussionThese findings provide a foundation for further molecular investigations into wheat meiosis regulation to fully understand the underlying mechanisms of how TaRecQ4 affects chiasma formation, as well as to identify ways to mitigate these defects and enhance both homologous and homoeologous recombination efficiency in wheat.

Dataset Information

Network Rewiring of Homologous Recombination Enzymes during Mitotic Proliferation and Meiosis.

Publications

Network Rewiring of Homologous Recombination Enzymes during Mitotic Proliferation and Meiosis.

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