Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia.

摘要: We and others have shown that the dysregulation of DNA repair pathways can contribute to phenomenon hypoxia-induced genetic instability within tumor microenvironment. Several studies revealed recombinational genes, RAD51 BRCA1, mismatch MLH1 MSH2, are decreased in expression response hypoxic stress, prompting interest elucidating mechanistic basis for these responses. Here we report downregulation by hypoxia is specifically mediated repressive E2F4/p130 complexes bind a single E2F site proximal promoter gene. Intriguingly, this conserved BRCA1 gene, which also regulated similar mechanism hypoxia. Mechanistically, found induces substantial p130 dephosphorylation nuclear accumulation, leading formation increased occupancy E2F4 at promoters. These findings reveal coordinated transcriptional program represents an integral stress. In addition, co-regulation key factors homology-dependent pathway provides further understanding tumors may guide design new therapeutic strategies cancer.