DNA double-strand breaks (DSBs) are cytotoxic damages that can be repaired either by the
homologous recombinational repair (HR) pathway or by the
non-homologous end-joining (NHEJ) pathway. NHEJ, although faster than HR, is less accurate. The early divergent step between the two pathways is end resection, and this step is regulated by numerous factors. In particular,
BRCA1 and 53BP1 play a role in determining the balance between the two pathways. 53BP1 restricts resection and promotes NHEJ.
Age-associated deficient repair Ordinarily during the
G1 phase of the
cell cycle, when a
sister chromatid is unavailable for HR,
NHEJ is the predominant pathway for
repairing DNA double-strand breaks (DSBs). However, as individuals age, recruitment of 53BP1 to DSBs during G1 becomes deficient. The absence of 53BP1 at such DSBs appears to promote the alternative error-prone repair process Alt-EJ. This repair process, also referred to as
microhomology-mediated end joining, is highly inaccurate and likely contributes to the aging process. == Interactions ==