FAAP100 is required for the resolution of transcription-replication conflicts in primordial germ cells
Year: 2023
Type: article
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.
Source: BMC Biology
Authors: Weiwei Xu, Yajuan Yang, Yongze Yu, Canxin Wen, Simin Zhao, Lili Cao, Shidou Zhao, Yingying Qin, Zi-Jiang Chen
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,290
Funders: Shandong University, National Natural Science Foundation of China, Chinese Academy of Sciences, Natural Science Foundation of Shandong Province, Institute of Zoology, Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, National Key Research and Development Program of China
OpenAlex ID: W4385797597