MCM9 deficiency delays primordial germ cell proliferation independent of the ATM pathway.

摘要: Maintenance of genome integrity is crucial for the germline, and this reflected by lower mutation rates in gametes than somatic cells. Germ cells at different stages employ DNA damage response (DDR) mechanisms. In to certain repair defects, primordial germ (PGCs) either undergo apoptosis or delayed proliferation, although little known about underlying mechanisms that govern these outcomes. Here, we report genetic studies DDR pathways underlie cell depletion mice mutant minichromosome maintenance 9 (Mcm9), a gene plays role homologous recombination (HRR). result reduced PGC numbers both before after they arrive primitive gonads. This reduction was attributable not apoptosis, independent ATM-CHK2-TRP53-P21 signaling. mechanism differs from Fancm mutants, which also display partially orchestrated ATM-TRP53-P21 pathway. doubly deficient FANCM MCM9 additive, indicating caused each triggers slow cycle as means preserve genomic integrity. genesis 53:678-684, 2015. © 2015 Wiley Periodicals, Inc.