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

First Author  Gray S Year  2020
Journal  Cell Rep Volume  32
Issue  1 Pages  107858
PubMed ID  32640224 Mgi Jnum  J:305619
Mgi Id  MGI:6706081 Doi  10.1016/j.celrep.2020.107858
Citation  Gray S, et al. (2020) Cyclin N-Terminal Domain-Containing-1 Coordinates Meiotic Crossover Formation with Cell-Cycle Progression in a Cyclin-Independent Manner. Cell Rep 32(1):107858
abstractText  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.
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