ArticleMolecular biology of the cell2009
The Cyclin-dependent kinase inhibitor Dacapo promotes genomic stability during premeiotic S phase.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
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- A mosaic genetic screen for genes involved in the early steps of Drosophila oogenesis.G3 (Bethesda, Md.) · 2013Article
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- Cyclin E controls Drosophila female germline stem cell maintenance independently of its role in proliferation by modulating responsiveness to niche signals.Development (Cambridge, England) · 2013Article
- Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline.Development (Cambridge, England) · 2011Article
- Reduced cul-5 activity causes aberrant follicular morphogenesis and germ cell loss in Drosophila oogenesis.PloS one · 2010Article
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
The proper execution of premeiotic S phase is essential to both the maintenance of genomic integrity and accurate chromosome segregation during the meiotic divisions. However, the regulation of premeiotic S phase remains poorly defined in metazoa. Here, we identify the p21(Cip1)/p27(Kip1)/p57(Kip2)-like cyclin-dependent kinase inhibitor (CKI) Dacapo (Dap) as a key regulator of premeiotic S phase and genomic stability during Drosophila oogenesis. In dap(-/-) females, ovarian cysts enter the meiotic cycle with high levels of Cyclin E/cyclin-dependent kinase (Cdk)2 activity and accumulate DNA damage during the premeiotic S phase. High Cyclin E/Cdk2 activity inhibits the accumulation of the replication-licensing factor Doubleparked/Cdt1 (Dup/Cdt1). Accordingly, we find that dap(-/-) ovarian cysts have low levels of Dup/Cdt1. Moreover, mutations in dup/cdt1 dominantly enhance the dap(-/-) DNA damage phenotype. Importantly, the DNA damage observed in dap(-/-) ovarian cysts is independent of the DNA double-strands breaks that initiate meiotic recombination. Together, our data suggest that the CKI Dap promotes the licensing of DNA replication origins for the premeiotic S phase by restricting Cdk activity in the early meiotic cycle. Finally, we report that dap(-/-) ovarian cysts frequently undergo an extramitotic division before meiotic entry, indicating that Dap influences the timing of the mitotic/meiotic transition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.