4XVM

Binary complex of human polymerase nu and DNA with the finger domain closed and thumb domain rotated out

Summary for 4XVM

• Entry DOI: 10.2210/pdb4xvm/pdb
• Related: 4XVI 4XVK 4XVL
• Descriptor: DNA polymerase nu, DNA (5'-D(*CP*TP*AP*GP*CP*GP*TP*CP*A)-3'), DNA (5'-D(*GP*AP*TP*CP*TP*GP*AP*CP*GP*CP*TP*AP*G)-3') (3 entities in total)
• Functional Keywords: pol nu, polymerase, error-prone dna synthesis, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 81482.56

Authors

Lee, Y.-S.,Yang, W. (deposition date: 2015-01-27, release date: 2015-03-11, Last modification date: 2023-09-27)

Primary citation

Lee, Y.S.,Gao, Y.,Yang, W.
How a homolog of high-fidelity replicases conducts mutagenic DNA synthesis.
Nat.Struct.Mol.Biol., 22:298-303, 2015

PubMed Abstract: All DNA replicases achieve high fidelity by a conserved mechanism, but each translesion polymerase carries out mutagenic DNA synthesis in its own way. Here we report crystal structures of human DNA polymerase ν (Pol ν), which is homologous to high-fidelity replicases yet is error prone. Instead of a simple open-to-closed movement of the O helix upon binding of a correct incoming nucleotide, Pol ν has a different open state and requires the finger domain to swing sideways and undergo both opening and closing motions to accommodate the nascent base pair. A single-amino acid substitution in the O helix of the finger domain improves the fidelity of Pol ν nearly ten-fold. A unique cavity and the flexibility of the thumb domain allow Pol ν to generate and accommodate a looped-out primer strand. Primer loop-out may be a mechanism for DNA trinucloetide-repeat expansion.

PubMed: 25775266
DOI: 10.1038/nsmb.2985

Experimental method

X-RAY DIFFRACTION (3.2 Å)