5AGA

Crystal structure of the Helicase domain of human DNA polymerase theta in complex with AMPPNP

Summary for 5AGA

• Entry DOI: 10.2210/pdb5aga/pdb
• Descriptor: DNA POLYMERASE THETA, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, CITRATE ANION, ... (6 entities in total)
• Functional Keywords: transferase, polq, dna repair
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus : O75417
• Total number of polymer chains: 1
• Total formula weight: 93959.89

Authors

Newman, J.A.,Cooper, C.D.O.,Aitkenhead, H.,Pinkas, D.M.,Kupinska, K.,Burgess-Brown, N.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.,Bountra, C.,Gileadi, O. (deposition date: 2015-01-29, release date: 2015-02-25, Last modification date: 2024-11-20)

Primary citation

Newman, J.A.,Cooper, C.D.O.,Aitkenhead, H.,Gileadi, O.
Structure of the Helicase Domain of DNA Polymerase Theta Reveals a Possible Role in the Microhomology-Mediated End-Joining Pathway.
Structure, 23:2319-, 2015

PubMed 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.

PubMed: 26636256
DOI: 10.1016/J.STR.2015.10.014

Experimental method

X-RAY DIFFRACTION (2.9 Å)