Transcription-replication conflicts in primordial germ cells necessitate the Fanconi anemia pathway to safeguard genome stability.

ABSTRACT: Preserving a high degree of genome integrity and stability in germ cells is of utmost importance for reproduction and species propagation. However, the regulatory mechanisms of maintaining genome stability in the developing primordial germ cells (PGCs), in which rapid proliferation is coupled with global hypertranscription, remain largely unknown. Here, we find that mouse PGCs encounter a constitutively high frequency of transcription-replication conflicts (TRCs), which lead to R-loop accumulation and impose endogenous replication stress on PGCs. We further demonstrate that the Fanconi anemia (FA) pathway is activated by TRCs and has a central role in the coordination between replication and transcription in the rapidly proliferating PGCs, as disabling the FA pathway leads to TRC and R-loo

SUBMITTER: Yang Y 

PROVIDER: S-EPMC9407672 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature