Is NHEJ a tumor suppressor or an aging suppressor?
… Nonhomologous end joining (NHEJ) is considered a caretaker since it repairs DNA double-strand breaks that would otherwise lead to gross chromosomal rearrangements (GCRs). NHEJ-mutant mice display increased GCRs, but without increased cancer. Instead these mice show early aging. This commentary focuses on the role NHEJ has on aging and cancer. I propose that NHEJ evolved to reduce GCRs and moderate gatekeeper responses that would otherwise cause early aging. Furthermore, NHEJ did not evolve to suppress tumors and any observed tumor suppression is merely circumstantial to unnatural laboratory conditions coupled with human bias that favors defining all DNA repair pathways as caretakers. If it does turn out that NHEJ mutants have increased genomic rearrangements and also increasing transcriptional noise, it could go a long way toward bolstering the theory of aging described above.
