Evidence map›Paper›PMID 16574152›Full record

ArticleJournal of molecular biology2006

A novel processive mechanism for DNA synthesis revealed by structure, modeling and mutagenesis of the accessory subunit of human mitochondrial DNA polymerase.

Li Fan, Sangbumn Kim, Carol L Farr, Kevin T Schaefer, Kathleen M Randolph, John A Tainer, Laurie S Kaguni

Abstract read
In one paragraph

Article in Journal of molecular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
2.2field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 72 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Structural basis for DNA proofreading.Nature communications · 2023
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
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  19. Article
  20. Human mitochondrial DNA replication machinery and disease.Current opinion in genetics & development · 2016
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Li FanLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92034, USA.
Sangbumn Kim
Carol L Farr
Kevin T Schaefer
Kathleen M Randolph
John A Tainer
Laurie S Kaguni
Michigan State University · USLawrence Berkeley National Laboratory · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Mitochondrial DNA Replisome: Mechanism, Structure and PhysiologyR01GM045295 · NIGMS · MICHIGAN STATE UNIVERSITY · PI KAGUNI, LAURIE SIMON · 1991 to 2013
$4.0M
NCI NIH HHS CA92584NCI NIH HHS P01 CA092584NIGMS NIH HHS GM45295NIGMS NIH HHS R01 GM045295
6 · The paper itself

Abstract

Mitochondrial DNA polymerase (pol gamma) is the sole DNA polymerase responsible for replication and repair of animal mitochondrial DNA. Here, we address the molecular mechanism by which the human holoenzyme achieves high processivity in nucleotide polymerization. We have determined the crystal structure of human pol gamma-beta, the accessory subunit that binds with high affinity to the catalytic core, pol gamma-alpha, to stimulate its activity and enhance holoenzyme processivity. We find that human pol gamma-beta shares a high level of structural similarity to class IIa aminoacyl tRNA synthetases, and forms a dimer in the crystal. A human pol gamma/DNA complex model was developed using the structures of the pol gamma-beta dimer and the bacteriophage T7 DNA polymerase ternary complex, which suggests multiple regions of subunit interaction between pol gamma-beta and the human catalytic core that allow it to encircle the newly synthesized double-stranded DNA, and thereby enhance DNA binding affinity and holoenzyme processivity. Biochemical properties of a novel set of human pol gamma-beta mutants are explained by and test the model, and elucidate the role of the accessory subunit as a novel type of processivity factor in stimulating pol gamma activity and in enhancing processivity.

Indexed as

Amino Acid SequenceAmino Acid SubstitutionBase SequenceCatalytic DomainCrystallography, X-RayDimerizationDNADNA-Directed DNA PolymeraseDNA Polymerase betaDNA Polymerase gammaHumansIn Vitro TechniquesMacromolecular SubstancesMitochondriaModels, MolecularMolecular Sequence DataDNADNA-Directed DNA PolymeraseDNA Polymerase betaDNA Polymerase gammaMacromolecular SubstancesPOLG protein, humanProtein Subunits

Identifiers

PMID16574152
PMCPMC4703138
OpenAlexW2028129061

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.