Dataset Information

Cyclin N-Terminal Domain-Containing-1 Coordinates Meiotic Crossover Formation with Cell-Cycle Progression in a Cyclin-Independent Manner.

ABSTRACT: During mammalian meiotic prophase I, programmed DNA double-strand breaks are repaired by non-crossover or crossover events, the latter predominantly occurring via the class I crossover pathway and requiring the cyclin N-terminal domain-containing 1(CNTD1) protein. Using an epitope-tagged Cntd1 allele, we detect a short isoform of CNTD1 in vivo that lacks a predicted N-terminal cyclin domain and does not bind cyclin-dependent kinases. Instead, we find that the short-form CNTD1 variant associates with components of the replication factor C (RFC) machinery to facilitate crossover formation, and with the E2 ubiquitin conjugating enzyme, CDC34, to regulate ubiquitylation and subsequent degradation of the WEE1 kinase, thereby modulating cell-cycle progression. We propose that these interactions facilitate a role for CNTD1 as a stop-go regulator during prophase I, ensuring accurate and complete crossover formation before allowing metaphase progression and the first meiotic division.

SUBMITTER: Gray S

PROVIDER: S-EPMC7341696 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cyclin N-Terminal Domain-Containing-1 Coordinates Meiotic Crossover Formation with Cell-Cycle Progression in a Cyclin-Independent Manner.

Gray Stephen S Santiago Emerson R ER Chappie Joshua S JS Cohen Paula E PE

Cell reports 20200701 1

During mammalian meiotic prophase I, programmed DNA double-strand breaks are repaired by non-crossover or crossover events, the latter predominantly occurring via the class I crossover pathway and requiring the cyclin N-terminal domain-containing 1(CNTD1) protein. Using an epitope-tagged Cntd1 allele, we detect a short isoform of CNTD1 in vivo that lacks a predicted N-terminal cyclin domain and does not bind cyclin-dependent kinases. Instead, we find that the short-form CNTD1 variant associates ...[more]

PMID: 32640224

Similar Datasets

Project description:Meiotic chromosome segregation relies on homologous chromosomes being linked by at least one crossover, the obligate crossover. Homolog pairing, synapsis and meiosis specific DNA repair mechanisms are required for crossovers but how they are coordinated to promote the obligate crossover is not well understood. PCH-2 is a highly conserved meiotic AAA+-ATPase that has been assigned a variety of functions; whether these functions reflect its conserved role has been difficult to determine. We show that PCH-2 restrains pairing, synapsis and recombination in C. elegans. Loss of pch-2 results in the acceleration of synapsis and homolog-dependent meiotic DNA repair, producing a subtle increase in meiotic defects, and suppresses pairing, synapsis and recombination defects in some mutant backgrounds. Some defects in pch-2 mutants can be suppressed by incubation at lower temperature and these defects increase in frequency in wildtype worms grown at higher temperature, suggesting that PCH-2 introduces a kinetic barrier to the formation of intermediates that support pairing, synapsis or crossover recombination. We hypothesize that this kinetic barrier contributes to quality control during meiotic prophase. Consistent with this possibility, defects in pch-2 mutants become more severe when another quality control mechanism, germline apoptosis, is abrogated or meiotic DNA repair is mildly disrupted. PCH-2 is expressed in germline nuclei immediately preceding the onset of stable homolog pairing and synapsis. Once chromosomes are synapsed, PCH-2 localizes to the SC and is removed in late pachytene, prior to SC disassembly, correlating with when homolog-dependent DNA repair mechanisms predominate in the germline. Indeed, loss of pch-2 results in premature loss of homolog access. Altogether, our data indicate that PCH-2 coordinates pairing, synapsis and recombination to promote crossover assurance. Specifically, we propose that the conserved function of PCH-2 is to destabilize pairing and/or recombination intermediates to slow their progression and ensure their fidelity during meiotic prophase.

Dataset Information

Cyclin N-Terminal Domain-Containing-1 Coordinates Meiotic Crossover Formation with Cell-Cycle Progression in a Cyclin-Independent Manner.

Publications

Cyclin N-Terminal Domain-Containing-1 Coordinates Meiotic Crossover Formation with Cell-Cycle Progression in a Cyclin-Independent Manner.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets