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

Gray, Stephen; Santiago, Emerson R.; Chappie, Joshua S.; Cohen, Paula E.

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.

Citation

Gray, S., Santiago, E. R., Chappie, J. S., & Cohen, P. E. (2020). Cyclin N-Terminal Domain-Containing-1 Coordinates Meiotic Crossover Formation with Cell-Cycle Progression in a Cyclin-Independent Manner. Cell Reports, 32(1), Article 107858. https://doi.org/10.1016/j.celrep.2020.107858

• Journal Article Type: Article
• Acceptance Date: Jun 12, 2020
• Online Publication Date: Jul 7, 2020
• Publication Date: Jul 7, 2020
• Deposit Date: Jul 10, 2020
• Publicly Available Date: Jul 13, 2020
• Journal: Cell Reports
• Print ISSN: 2211-1247
• Electronic ISSN: 2211-1247
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 32
• Issue: 1
• Article Number: 107858
• DOI: https://doi.org/10.1016/j.celrep.2020.107858
• Keywords: General Biochemistry, Genetics and Molecular Biology
• Public URL: https://nottingham-repository.worktribe.com/output/4758677
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2211124720308391?dgcid=rss_sd_all