Journal article
The C-terminal region of translesion synthesis DNA polymerase η is partially unstructured and has high conformational flexibility
Nucleic acids research, Vol.46(4), pp.2107-2120
02/28/2018
DOI: 10.1093/nar/gky031
PMCID: PMC5829636
PMID: 29385534
Abstract
Eukaryotic DNA polymerase η catalyzes translesion synthesis of thymine dimers and 8-oxoguanines. It is comprised of a polymerase domain and a C-terminal region, both of which are required for its biological function. The C-terminal region mediates interactions with proliferating cell nuclear antigen (PCNA) and other translesion synthesis proteins such as Rev1. This region contains a ubiquitin-binding/zinc-binding (UBZ) motif and a PCNA-interacting protein (PIP) motif. Currently little structural information is available for this region of polymerase η. Using a combination of approaches—including genetic complementation assays, X-ray crystallography, Langevin dynamics simulations, and small-angle X-ray scattering—we show that the C-terminal region is partially unstructured and has high conformational flexibility. This implies that the C-terminal region acts as a flexible tether linking the polymerase domain to PCNA thereby increasing its local concentration. Such tethering would facilitate the sampling of translesion synthesis polymerases to ensure that the most appropriate one is selected to bypass the lesion.
Details
- Title: Subtitle
- The C-terminal region of translesion synthesis DNA polymerase η is partially unstructured and has high conformational flexibility
- Creators
- Kyle T Powers - University of IowaAdrian H Elcock - University of IowaM Todd Washington - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nucleic acids research, Vol.46(4), pp.2107-2120
- DOI
- 10.1093/nar/gky031
- PMID
- 29385534
- PMCID
- PMC5829636
- ISSN
- 0305-1048
- eISSN
- 1362-4962
- Grant note
- DOI: 10.13039/100000057, name: National Institute of General Medicine, award: GM081433, GM087290
- Language
- English
- Date published
- 02/28/2018
- Academic Unit
- Physics and Astronomy; Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984293084502771
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