Fance deficiency inhibits primordial germ cell proliferation associated with transcription-replication conflicts accumulate and DNA repair defects.

ABSTRACT: Fanconi anemia (FA) gene mutations are critical components in the genetic etiology of premature ovarian insufficiency (POI). Fance^-/- mice detected meiotic arrest of primordial germ cells (PGCs) as early as embryonic day (E) 13.5 and exhibited decreased ovarian reserve after birth. However, the mechanism of Fance defect leading to dysgenesis of PGCs is unclear. We aimed to explore the effect of Fance defects on mitotic proliferation of PGCs. Combined with transcriptomic sequencing and validation, we examined the effect of Fance defects on cell cycle, transcription-replication conflicts (TRCs), and multiple DNA repair pathways in PGCs during active DNA replication at E11.5 and E12.5. Results showed Fance defects cause decreased numbers of PGCs during rapid mitosis at E11.5 and E1

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC10416540 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature