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Publication : Maternal DCAF2 is crucial for maintenance of genome stability during the first cell cycle in mice.

First Author  Xu YW Year  2017
Journal  J Cell Sci Volume  130
Issue  19 Pages  3297-3307
PubMed ID  28818995 Mgi Jnum  J:245637
Mgi Id  MGI:5914541 Doi  10.1242/jcs.206664
Citation  Xu YW, et al. (2017) Maternal DCAF2 is crucial for maintenance of genome stability during the first cell cycle in mice. J Cell Sci 130(19):3297-3307
abstractText  Precise regulation of DNA replication and genome integrity is crucial for gametogenesis and early embryogenesis. Cullin ring-finger ubiquitin ligase 4 (CRL4) has multiple functions in the maintenance of germ cell survival, oocyte meiotic maturation, and maternal-zygotic transition in mammals. DDB1-cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2) is an evolutionarily conserved substrate receptor of CRL4. To determine whether DCAF2 is a key CRL4 substrate adaptor in mammalian oocytes, we generated a novel mouse strain that carries a Dcaf2 allele flanked by loxP sequences, and specifically deleted Dcaf2 in oocytes. Dcaf2 knockout in mouse oocytes leads to female infertility. Although Dcaf2-null oocytes were able to develop and mature normally, the embryos derived from them were arrested at one- to two-cell stage, owing to prolonged DNA replication and accumulation of massive DNA damage. These results indicate that DCAF2 is a previously unrecognized maternal factor that safeguards zygotic genome stability. Maternal DCAF2 protein is crucial for prevention of DNA re-replication in the first and unique mitotic cell cycle of the zygote.This article has an associated First Person interview with the first author of the paper.
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