Fig. 1.

Overview of repair mechanisms of DNA double-strand breaks (DSDBs). A. Non-homologous end joining repair (NHEJ) is a compact process of re-ligation of the broken DNA ends that requires minimal processing and does not require a template. It occurs throughout the cell cycle. NHEJ is initiated by the binding of the Ku 70–80 heterodimer, one of the subunits of DNA-PK to the double stranded DNA ends to protect it from nuclease digestion. DNA-bound Ku recruits the DNA-protein kinase catalytic subunit (DNA-PKcs), generating the DNA-PK complex which predominantly regulates NHEJ through autophosphorylation and facilitates recruitment of a ligation complex, which encompasses X-ray cross complementing Group 4 (XRCC4) and DNA ligase 4. DNA-PKcs further activate Artemis nuclease which cleave the DNA overhangs. The DNA polymerase λ or μ facilitates the DNA synthesis followed by ligation of the DNA gaps. B. Homologous recombination (HR) DNA repair is a predominantly accurate process that uses a sister chromatid as a template for DSDB repair and functions only in late S/G2 phase. DNA breaks are initially recognized by MRN complex which together with BRCA1and CtIP generates ssDNA overhangs. These overhangs are coated with replication protein A (RPA) which are then exchanged for RAD51 where BRCA1/2 assist the exchange. RAD51 loading promotes invasion onto the undamaged template and strand exchange followed by ligation of the DNA ends. RAD51 paralogues (RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3) assist RAD51 in the HR DNA repair process. The DNA synthesis is performed by polymerase δ or ε.