4X0Q

Ternary complex of human DNA polymerase theta C-terminal domain binding ddGTP opposite dCMP

Summary for 4X0Q

• Entry DOI: 10.2210/pdb4x0q/pdb
• Related: 4X0P
• Descriptor: DNA polymerase theta, DNA (5'-D(*CP*GP*TP*CP*CP*AP*AP*TP*GP*AP*CP*AP*G)-3'), DNA (5'-D(P*CP*TP*GP*TP*CP*AP*TP*TP*G)-3'), ... (6 entities in total)
• Functional Keywords: dna polymerase, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 193182.16

Authors

Zahn, K.E.,Doublie, S. (deposition date: 2014-11-22, release date: 2015-03-18, Last modification date: 2023-09-27)

Primary citation

Zahn, K.E.,Averill, A.M.,Aller, P.,Wood, R.D.,Doublie, S.
Human DNA polymerase theta grasps the primer terminus to mediate DNA repair.
Nat.Struct.Mol.Biol., 22:304-311, 2015

PubMed Abstract: DNA polymerase θ protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks. Polymerase θ is overexpressed in breast, lung and oral cancers, and reduction of its activity in mammalian cells increases sensitivity to double-strand break-inducing agents, including ionizing radiation. Reported here are crystal structures of the C-terminal polymerase domain from human polymerase θ, illustrating two potential modes of dimerization. One structure depicts insertion of ddATP opposite an abasic-site analog during translesion DNA synthesis. The second structure describes a cognate ddGTP complex. Polymerase θ uses a specialized thumb subdomain to establish unique upstream contacts to the primer DNA strand, including an interaction with the 3'-terminal phosphate from one of five distinctive insertion loops. These observations demonstrate how polymerase θ grasps the primer to bypass DNA lesions or extend poorly annealed DNA termini to mediate end-joining.

PubMed: 25775267
DOI: 10.1038/nsmb.2993

Experimental method

X-RAY DIFFRACTION (3.9 Å)