Classical non-homologous end joining (C_NHEJ) eliminates DNA double-strand breaks (DSBs) by direct ligation without the need for a homologous template, in contrast to homologous recombination. C_NHEJ typically utilizes short homologous DNA sequences at the end of the broken DNA helix to hook and join the two ends together. When the overhangs are perfectly compatible, C_NHEJ repairs the break accurately. When the overhangs are not compatible or the break has sharp ends, imprecise repair leads to loss of nucleotides and to deletions. C_NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs processing of ends, and recruitment of the DNA ligase IV (LIG4)-XRCC4 complex, which brings about ligation. This is the predominant double-strand break repair pathway in mammalian cells tha is active through the cell cycle.
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