6wie
From Proteopedia
Post-catalytic nicked complex of human Polymerase Mu on a complementary DNA double-strand break substrate
Structural highlights
FunctionDPOLM_HUMAN Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.[1] [2] [3] [4] Publication Abstract from PubMedGenomic integrity is threatened by cytotoxic DNA double-strand breaks (DSBs), which must be resolved efficiently to prevent sequence loss, chromosomal rearrangements/translocations, or cell death. Polymerase mu (Polmu) participates in DSB repair via the nonhomologous end-joining (NHEJ) pathway, by filling small sequence gaps in broken ends to create substrates ultimately ligatable by DNA Ligase IV. Here we present structures of human Polmu engaging a DSB substrate. Synapsis is mediated solely by Polmu, facilitated by single-nucleotide homology at the break site, wherein both ends of the discontinuous template strand are stabilized by a hydrogen bonding network. The active site in the quaternary Pol mu complex is poised for catalysis and nucleotide incoporation proceeds in crystallo. These structures demonstrate that Polmu may address complementary DSB substrates during NHEJ in a manner indistinguishable from single-strand breaks. Structural snapshots of human DNA polymerase mu engaged on a DNA double-strand break.,Kaminski AM, Pryor JM, Ramsden DA, Kunkel TA, Pedersen LC, Bebenek K Nat Commun. 2020 Sep 22;11(1):4784. doi: 10.1038/s41467-020-18506-5. PMID:32963245[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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