Aged people get more cancers than young ones due to use of Non-homologous end joining instead of homologous recombination for repairing double strand breaks

Double stranded breaks are the most dangerous form of DNA damage occurring in the genome. Double strand breaks are caused by internal agents like reactive oxygen species and many external agents like radiation.  Replication errors also cause double strand breaks.   Living organisms have two methods for correcting this error: Homologous recombination(HR) found both in bacteria and eukaryotes and non-homologous end joining (NHEJ) found mostly in eukaryotes. HR is a method which corrects the double strand breaks by using the homologous chromosome as the reference (this is the reason for diploid nature of most eukaryotes). Except for gene conversion, it does not cause mutation  to the genes in which the double strand break has occurred (usually broken ends have damaged bases which are removed  and correct bases are added by HR using the homologous chromosome as the template). But NHEJ just joins the broken ends without replacing the damaged bases (as it does not have a template to refer) leading to mutation of the genes in which double strand breaks occurred.



It was not clear when HR is used and when NHEJ is used for repairing double stranded DNA breaks. Use of either of these methods has great implication on the health of the organisms.  In a recent research  work published in PNAS it has been shown that  in humans HR declines sharply with increasing replicative age, with an up to 38-fold decrease in efficiency in presenescent cells relative to young cells. This decline is not explained by a reduction of the number of cells in S/G2/M stage as presenescent cells are actively dividing. Results of this study using normal human fibroblasts with a chromosomally  integrated  HR cassette  showed   that in aging cells, the precise HR pathway becomes repressed giving way to a more error-prone NHEJ pathway. These changes in the processing of DSBs may contribute to age-related genomic instability and a higher incidence of cancer with age.

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