Cited by 150DNA Repair MechanismsEnzyme Structure and FunctionMitochondrial Function and Pathology

Crystal Structure and Deletion Analysis Show that the Accessory Subunit of Mammalian DNA Polymerase γ, PolγB, Functions as a Homodimer

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Carrodeguas, José A., Theis, Karsten, Bogenhagen, Daniel F., Kisker, Caroline·2001·Molecular Cell

Abstract

Polymerase gamma, which replicates and repairs mitochondrial DNA, requires the Pol gamma B subunit for processivity. We determined the crystal structure of mouse Pol gamma B, a core component of the mitochondrial replication machinery. Pol gamma B shows high similarity to glycyl-tRNA synthetase and dimerizes through an unusual intermolecular four-helix bundle. A human Pol gamma B mutant lacking the four-helix bundle failed to dimerize in solution or to stimulate the catalytic subunit Pol gamma A, but retained the ability to bind with Pol gamma A to a primer-template construct, indicating that the functional holoenzyme contains two Pol gamma B molecules. Other mutants retained stimulatory activity but lost the ability to bind folded ssDNA. These results suggest that the Pol gamma B dimer contains distinct sites for Pol gamma A binding, dimerization, and DNA binding.

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Crossref · 10.1016/s1097-2765(01)00153-8

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Authors
Carrodeguas, J. A., Theis, K., Bogenhagen, D. F., & Kisker, C.
Affiliations
Stony Brook University (US)
Corresponding author
Kisker, Caroline
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2001-01
Volume
7
Issue
1
Pages
43-54
ISSN
1097-2765 (ISSN-L)
OpenAlex
W1978422652
Cited by
150
References
54
Citations by year
2025: 3 · 2024: 3 · 2023: 2 · 2021: 1 · 2020: 7 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 10 · 2015: 10 · 2014: 1 · 2013: 4 · 2012: 8
FWCI
4.66
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM029681, GM581980, GM29681)
  • National Institute of Environmental Health Sciences (ES04068, P01ES004068)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
DNA polymerase gamma, auxiliary subunits, homodimer, four-helix bundle, mitochondrial DNA replication, DNA repair, polymerase processivity, DNA binding, crystal structure, deletion mutants
MeSH terms
DNA Polymerase gamma, Amino Acid Sequence, Animals, Binding Sites, Crystallography, DNA-Directed DNA Polymerase, DNA Replication, DNA, Single-Stranded, Glycine-tRNA Ligase, Humans, Mammals, Mitochondria, Molecular Sequence Data, Surface Properties, Water, Gene Deletion, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Folding, Dimerization, Mice

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