DNA repair protein FANCD2 has both ubiquitination-dependent and ubiquitination-independent functions during germ cell development
Simin Zhao, Chengzi Huang, Yajuan Yang, Weiwei Xu, Yongze Yu, Canxin Wen, Lili Cao, Fei Gao, Yingying Qin, Zi‐Jiang Chen, Ting Guo, Shidou Zhao
Abstract
) mice. We showed that in the embryonic stage, both the ubiquitination-dependent and ubiquitination-independent functions of FANCD2 were required for the expansion of primordial germ cells and establishment of the reproductive reserve by reducing transcription-replication conflicts and thus maintaining genome stability in primordial germ cells. Furthermore, we found that during meiosis in spermatogenesis, FANCD2 promoted chromosome synapsis and regulated crossover formation independently of its ubiquitination, but that both ubiquitinated and nonubiquitinated FANCD2 functioned in programmed double strand break repair. Finally, we revealed that on meiotic XY chromosomes, H3K4me2 accumulation required ubiquitination-independent functionality of FANCD2, while the regulation of H3K9me2 and H3K9me3 depended on FANCD2 ubiquitination. Taken together, our findings suggest that FANCD2 has distinct functions that are both dependent on and independent of its ubiquitination during germ cell development.