Influence of donor age on cellular ability to carry out DNA repair via homologous recombination

Abstract

Cells from old and young donors differ in their abilities for homologous recombination in vitro, which is distinctly visible at the stage of convergence of the homologous chromosomes. We hypothesize that this effect contributes to genome instability and aging. Cells from donors 70 years and older have a limited ability for homologous recombination induced by X-ray irradiation. Interestingly, a repressor of RNA polymerase II, alpha-amanitin, induces homologous recombination when administered at physiologically toxic doses in cells from donors in all age groups, old and young, as well as in cells with genetic defects in the DNA repair system due to mutations in BRCA1 and BRCA2 genes. Furthermore, in BRCA1 and BRCA2 mutant cells, the effects of irradiation and alpha-amanitin damage are not integrated and do not increase the rate of homologous recombination.