The CDKN1B-RB1-E2F1 pathway protects mouse spermatogonial stem cells from genomic damage
Access this Article
Search this Article
Spermatogonial stem cells (SSCs) undergo self-renewal divisions to provide the foundation for spermatogenesis. Although <i>Rb1</i> deficiency is reportedly essential for SSC self-renewal, its mechanism has remained unknown. Here we report that <i>Rb1</i> is critical for cell cycle progression and protection of SSCs from DNA double-strand breaks (DSBs). Cultured SSCs depleted of <i>Cdkn1b</i> proliferated poorly and showed diminished expression of CDK4 and RB1, thereby leading to hypophosphorylation of RB1. <i>Rb1</i> deficiency induced cell cycle arrest and apoptosis in cultured SSCs, which expressed markers for DNA DSBs. This DNA damage is caused by increased E2F1 activity, the depletion of which decreased DNA DSBs caused by <i>Rb1</i> deficiency. Depletion of <i>Cdkn1a</i> and <i>Bbc3</i>, which were upregulated by <i>Trp53</i>, rescued <i>Rb1</i>-deficient cells from undergoing cell cycle arrest and apoptosis. These results suggest that the CDKN1B-RB1-E2F1 pathway is essential for SSC self-renewal and protects SSCs against genomic damage.
- Journal of Reproduction and Development
Journal of Reproduction and Development 61(4), 305-316, 2015
Society for Reproduction and Development