PDBsum entry 5a9j

Hydrolase

PDB id: 5a9j

Contents

Protein chains

805 a.a.

PDB id:

5a9j

Name:

Hydrolase

Title:

Crystal structure of the helicase domain of human DNA polymerase theta, apo-form

Structure:

DNA polymerase theta. Chain: a, b, c, d. Fragment: helicase domain, unp residues 1-894. Synonym: DNA polymerase eta. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

3.55Å R-factor: 0.227 R-free: 0.265

Authors:

J.A.Newman,C.D.O.Cooper,H.Aitkenhead,D.M.Pinkas,K.Kupinska,N.Burgess- Brown,F.Von Delft,C.H.Arrowsmith,A.Edwards,C.Bountra,O.Gileadi

Key ref:

J.A.Newman et al. (2015). Structure of the Helicase Domain of DNA Polymerase Theta Reveals a Possible Role in the Microhomology-Mediated End-Joining Pathway. Structure, 23, 2319-2330. PubMed id: 26636256 DOI: 10.1016/j.str.2015.10.014

Date:

21-Jul-15 Release date: 16-Dec-15

Protein chains

O75417  (DPOLQ_HUMAN) -  DNA polymerase theta from Homo sapiens

Seq: 2590 a.a.

Struc: 805 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 3: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 4: E.C.3.6.4.12 - Dna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.str.2015.10.014

Structure 23:2319-2330 (2015)

PubMed id: 26636256

Structure of the Helicase Domain of DNA Polymerase Theta Reveals a Possible Role in the Microhomology-Mediated End-Joining Pathway.

J.A.Newman, C.D.Cooper, H.Aitkenhead, O.Gileadi.

ABSTRACT

DNA polymerase theta (Polθ) has been identified as a crucial alternative non-homologous end-joining factor in mammalian cells. Polθ is upregulated in a range of cancer cell types defective in homologous recombination, and knockdown has been shown to inhibit cell survival in a subset of these, making it an attractive target for cancer treatment. We present crystal structures of the helicase domain of human Polθ in the presence and absence of bound nucleotides, and a characterization of its DNA-binding and DNA-stimulated ATPase activities. Comparisons with related helicases from the Hel308 family identify several unique features. Polθ exists as a tetramer both in the crystals and in solution. We propose a model for DNA binding to the Polθ helicase domain in the context of the Polθ tetramer, which suggests a role for the helicase domain in strand annealing of DNA templates for subsequent processing by the polymerase domain.