Summary information and primary citation

PDB-id
4yd1; SNAP-derived features in text and JSON formats; DNAproDB
Class
transferase-DNA
Method
X-ray (1.75 Å)
Summary
Ternary complex of human DNA polymerase mu with 2-nt gapped DNA substrate and an incoming nonhydrolyzable dumpnpp
Reference
Moon AF, Gosavi RA, Kunkel TA, Pedersen LC, Bebenek K (2015): "Creative template-dependent synthesis by human polymerase mu." Proc.Natl.Acad.Sci.USA, 112, E4530-E4536. doi: 10.1073/pnas.1505798112.
Abstract
Among the many proteins used to repair DNA double-strand breaks by nonhomologous end joining (NHEJ) are two related family X DNA polymerases, Pol λ and Pol µ. Which of these two polymerases is preferentially used for filling DNA gaps during NHEJ partly depends on sequence complementarity at the break, with Pol λ and Pol µ repairing complementary and noncomplementary ends, respectively. To better understand these substrate preferences, we present crystal structures of Pol µ on a 2-nt gapped DNA substrate, representing three steps of the catalytic cycle. In striking contrast to Pol λ, Pol µ "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.

Cartoon-block schematics in six views (download the tarball)

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