Hypersensitivity of Primordial Germ Cells to Compromised Replication-Associated DNA Repair Involves ATM-p53-p21 Signaling

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The precursors to sperm and eggs begin are a group of <100 cells in the embryo, called primordial germ cells (PGCs). They migrate in the primitive embryo to the location of the future gonads, then undergo a rapid proliferation over the next few days to a population of many thousands. Because these cells contain the precious genetic information for our offspring, and the DNA replication associated with rapid PGC proliferation is subject to spontaneous errors, mechanisms exist to avoid propagation of mutations. A manifestation of this is the high sensitivity of PGCs to genetic perturbations affecting DNA repair. We studied mice defective for a gene called Fanconi anemia M (Fancm) that is important for repair of DNA damage that occurs during replication. Although it is expressed in all tissues, only the PGCs are affected in mutants, and are reduced in number. We find that PGCs lacking Fancm respond by slowing cell division, and identified the genetic pathway responsible for this protective response.

Vyšlo v časopise: Hypersensitivity of Primordial Germ Cells to Compromised Replication-Associated DNA Repair Involves ATM-p53-p21 Signaling. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004471
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004471

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