Journal
BMC BIOLOGY
Volume 21, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12915-023-01676-1
Keywords
Primordial germ cells; FAAP100; Genome stability; Transcription-replication conflicts; R-loop
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The study reveals that FAAP100 is essential for resolving transcription-replication conflicts and protecting replication forks during the proliferation of mouse primordial germ cells. Its loss leads to DNA damage and insufficient reproductive reserve. This finding is important for understanding germ cell development and genetic stability maintenance.
BackgroundThe 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.ResultsWe 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.ConclusionsOur findings suggest that FAAP100 is required for the resolution of TRCs in PGCs to safeguard their genome stability.
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