Chapter 9 - DNA double-strand repair by nonhomologous end joining and its clinical relevance

Abstract

Emerging evidence indicates that nonhomologous end joining (NHEJ) is comprised primarily of canonical NHEJ and alternative NHEJ (or noncanonical NHEJ) pathways. The former pathway results in minimal processing of the DSB ends, whereas the latter process typically results in insertions and deletions, with or without local sequence microhomology. Canonical NHEJ is considered the major pathway for the repair of DSBs induced by ionizing radiation in human cells. Noncanonical NHEJ was initially thought of as a “backup” pathway, since it first was discovered in cNHEJ-deficient cells. More recent studies, however, suggest that it may actively compete with both canonical NHEJ and homologous recombination (HR). In this chapter we review the current understanding of the basic mechanisms and regulation of the NHEJ subpathways, highlighting those insights with clinical implications. We also present potential opportunities in which NHEJ inhibition may be utilized for selective tumor cell targeting.