FAAP100 is Required for the Resolution of Transcription-replication Conflicts in Primordial Germ Cells

Overview

Journal BMC Biol

Publisher Biomed Central

Specialty Biology

Date 2023 Aug 14

PMID 37580696

Authors

Weiwei Xu

Yajuan Yang

Yongze Yu

Canxin Wen

Simin Zhao

Lili Cao

Shidou Zhao

Yingying Qin

Zi-Jiang Chen

Affiliations

Soon will be listed here.

Abstract

Background: The maintenance of genome stability in primordial germ cells (PGCs) is crucial for the faithful transmission of genetic information and the establishment of reproductive reserve. Numerous studies in recent decades have linked the Fanconi anemia (FA) pathway with fertility, particularly PGC development. However, the role of FAAP100, an essential component of the FA core complex, in germ cell development is unexplored.

Results: We find that FAAP100 plays an essential role in R-loop resolution and replication fork protection to counteract transcription-replication conflicts (TRCs) during mouse PGC proliferation. FAAP100 deletion leads to FA pathway inactivation, increases TRCs as well as cotranscriptional R-loops, and contributes to the collapse of replication forks and the generation of DNA damage. Then, the activated p53 signaling pathway triggers PGC proliferation defects, ultimately resulting in insufficient establishment of reproductive reserve in both sexes of mice.

Conclusions: Our findings suggest that FAAP100 is required for the resolution of TRCs in PGCs to safeguard their genome stability.

Citing Articles

Primordial germ cell DNA demethylation and development require DNA translesion synthesis.

Shah P, Hill R, Dion C, Clark S, Abakir A, Willems J Nat Commun. 2024; 15(1):3734.

PMID: 38702312 PMC: 11068800. DOI: 10.1038/s41467-024-47219-2.

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