Alternative non-homologous end joining (A_NHEJ) is one of the pathways for repairing double-strand breaks in DNA. A_NHEJ is distinguished from the other repair mechanisms by search for the 5-25 base pair microhomologous sequences along the DNA sequence to align the broken strands before joining. Once aligned, any overhanging bases (flaps) and mismatched bases on the strands are removed and any missing nucleotides are inserted. A_NHEJ uses a Ku proteins and DNA-PK independent repair mechanism and active through the cell cycle. Proteins implicated in A_NHEJ are PARP1, the MRN complex and its partner CtIP, after the microhomology finding and filling in missing nucleotides by POLN or POLD or POLL the ends are rejoined either by LIG3 or LIG1. There is a competition between Ku (the initiator of C_NHEJ) and PARP1 (the initiator of A_NHEJ) for DSBs binding and the pre-existing C-NHEJ factors at the DSB compromise A_NHEJ. In most cases a cell uses A_NHEJ only when the C_NHEJ is impaired. A_NHEJ is an error-prone method of repair and always results in deletion mutations and may cause genomic instability and initiate the creation of oncogenes.
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