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DNA repair

Pol X DNA polymerases contribute to NHEJ flexibility

Nature Structural & Molecular Biology volume 30, pages 5–8 (2023)Cite this article

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New work on DNA polymerase λ highlights its remarkable flexibility. This fits with the generally adaptable nature of the DNA-repair process in which this enzyme is involved—nonhomologous end-joining—which allows this mechanism to handle diverse types of broken DNA ends in order to restore the duplex structure, albeit with a loss of information at the join.

For nearly all NHEJ joining events, XRCC4–DNA ligase IV (X4L4) carries out the ligation. Exceptions to this are observed in cells lacking XRCC4 or ligase IV and concomitantly when there is time for either of the other two ligases (ligase I (L1) and ligase III (L3)) to ligate either the top strand or the bottom strand of the DNA duplex3. This may occur in repetitive sequences when the top-strand and bottom-strand nicks are far enough apart to permit L1 or L3 to ligate either of the two strands. Once the top or bottom strand is ligated, then ligation of the antiparallel strand can be achieved by any ligase. Within cells, joining by L1 or L3 occurs more slowly than the normal repair of such breaks by X4L4 (ref. 3). For some processes—or for slowly dividing or nondividing cells—this may not cause a viability problem.

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Fig. 1: Choice of pathway for double-strand-break repair.
Fig. 2: General features of NHEJ.
Fig. 3: Additions of nucleotides by pol X family polymerases at DNA ends.

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Acknowledgements

M.R.L. is supported by National Interests of Health grants GM118009 and CA100504.

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  1. University of Southern California, Los Angeles, CA, USA

    Michael R. Lieber

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Correspondence to Michael R. Lieber.

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Lieber, M.R. Pol X DNA polymerases contribute to NHEJ flexibility. Nat Struct Mol Biol 30, 5–8 (2023). https://doi.org/10.1038/s41594-022-00904-6

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