4yd1
Ternary complex of human DNA Polymerase Mu with 2-nt gapped DNA substrate and an incoming nonhydrolyzable dUMPNPP
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 PubMedAmong the many proteins used to repair DNA double-strand breaks by nonhomologous end joining (NHEJ) are two related family X DNA polymerases, Pol lambda and Pol micro. Which of these two polymerases is preferentially used for filling DNA gaps during NHEJ partly depends on sequence complementarity at the break, with Pol lambda and Pol micro repairing complementary and noncomplementary ends, respectively. To better understand these substrate preferences, we present crystal structures of Pol micro on a 2-nt gapped DNA substrate, representing three steps of the catalytic cycle. In striking contrast to Pol lambda, Pol micro "skips" the first available template nucleotide, instead using the template base at the 5' end of the gap to direct nucleotide binding and incorporation. This remarkable divergence from canonical 3'-end gap filling is consistent with data on end-joining substrate specificity in cells, and provides insights into polymerase substrate choices during NHEJ. Creative template-dependent synthesis by human polymerase mu.,Moon AF, Gosavi RA, Kunkel TA, Pedersen LC, Bebenek K Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):E4530-6. doi:, 10.1073/pnas.1505798112. Epub 2015 Aug 3. PMID:26240373[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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