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, Dr. Heng-Yu Fan’s group at the Life Sciences Institute, Zhejiang University 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 1- to 2-cell stages 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 rereplication in the first and unique mitotic cell cycle of the zygote.

Working model of DCAF2 in the repair of DNA damage during embryo development.

This study was recently published by Journal of Cell Science. Doctoral graduate student Yi-Wen Xu is the first author of this paper.

Link: http://jcs.biologists.org/content/early/2017/08/16/jcs.206664