4YD1

Ternary complex of human DNA Polymerase Mu with 2-nt gapped DNA substrate and an incoming nonhydrolyzable dUMPNPP

Summary for 4YD1

• Entry DOI: 10.2210/pdb4yd1/pdb
• Related: 4YCX 4YD1
• Descriptor: DNA-directed DNA/RNA polymerase mu, SODIUM ION, DNA (5'-D(*CP*GP*GP*CP*AP*AP*TP*AP*CP*G)-3'), ... (11 entities in total)
• Functional Keywords: polymerase, dna repair, nhej, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 46294.03

Authors

Moon, A.F.,Gosavi, R.A.,Kunkel, T.A.,Pedersen, L.C.,Bebenek, K. (deposition date: 2015-02-20, release date: 2015-08-05, Last modification date: 2023-09-27)

Primary citation

Moon, A.F.,Gosavi, R.A.,Kunkel, T.A.,Pedersen, L.C.,Bebenek, K.
Creative template-dependent synthesis by human polymerase mu.
Proc.Natl.Acad.Sci.USA, 112:E4530-E4536, 2015

PubMed 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.

PubMed: 26240373
DOI: 10.1073/pnas.1505798112

Experimental method

X-RAY DIFFRACTION (1.75 Å)