Fanconi anemia pathway resolves transcription–replication conflicts in primordial germ cells

What is it about?

We reported that rapid proliferation coupled with global hypertranscription caused frequent occurrence of TRCs and consequent high levels of endogenous replication stress in mouse PGCs. We further demonstrated that the Fanconi anemia (FA) pathway was activated by TRCs in rapidly dividing PGCs, and played a central role in resolving TRCs through R-loop resolution and replication fork stabilization, thus enabling PGC rapid proliferation to establish a sufficient reproductive reserve. The findings suggest that the high frequency of TRCs underlies the increased requirement for the FA pathway to maintain genome stability of active proliferating PGCs.

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Why is it important?

This work provides insights into the unique genome feature of developing PGCs and helps to explain the reproductive defects in FA individuals.

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