Alternative pathways of non-homologous end joining (NHEJ) in genomic instability and cancer

An incompletely defined alternative non-homologous end joining pathway (A-NHEJ) frequently functioning as backup has recently been shown to process DNA double strand breaks (DSBs) when canonical cellular DSB repair activities are somehow compromised. While A-NHEJ offers survival advantage for the damaged cell, its propensity for large sequence alterations at the junction and the relatively frequent joining of unrelated DNA ends generates alterations in the genome that can have severe biological consequences. Indeed, evidence accumulates that A-NHEJ is a driver of the chromosomal rearrangements and the overall genomic instability that underpin the development of certain forms of cancer. Features of A-NHEJ causally related to these unfavorable outcomes are the apparent promiscuity in utilized factors and the delayed repair kinetics. The purpose of this review is to briefly summarize recent advances in our understanding regarding the function of A-NHEJ and to review emerging evidence for its role in oncogenic transformation.