6WIE

Post-catalytic nicked complex of human Polymerase Mu on a complementary DNA double-strand break substrate

Summary for 6WIE

• Entry DOI: 10.2210/pdb6wie/pdb
• Descriptor: DNA-directed DNA/RNA polymerase mu, PYROPHOSPHATE, DI(HYDROXYETHYL)ETHER, ... (14 entities in total)
• Functional Keywords: family x polymerase, nonhomologous end-joining, dna double-strand break repair, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 46383.82

Authors

Kaminski, A.M.,Kunkel, T.A.,Pedersen, L.C.,Bebenek, K. (deposition date: 2020-04-09, release date: 2020-10-07, Last modification date: 2023-10-18)

Primary citation

Kaminski, A.M.,Pryor, J.M.,Ramsden, D.A.,Kunkel, T.A.,Pedersen, L.C.,Bebenek, K.
Structural snapshots of human DNA polymerase mu engaged on a DNA double-strand break.
Nat Commun, 11:4784-4784, 2020

PubMed Abstract: Genomic 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 μ (Polμ) 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 Polμ engaging a DSB substrate. Synapsis is mediated solely by Polμ, 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 μ complex is poised for catalysis and nucleotide incoporation proceeds in crystallo. These structures demonstrate that Polμ may address complementary DSB substrates during NHEJ in a manner indistinguishable from single-strand breaks.

PubMed: 32963245
DOI: 10.1038/s41467-020-18506-5

Experimental method

X-RAY DIFFRACTION (1.5 Å)