Evidence map›Paper›PMID 29555682›Full record

ArticleThe Journal of biological chemistry2018

Activity and fidelity of human DNA polymerase α depend on primer structure.

Andrey G Baranovskiy, Vincent N Duong, Nigar D Babayeva, Yinbo Zhang, Youri I Pavlov, Karen S Anderson, Tahir H Tahirov

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
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

26 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Structures of human primosome elongation complexes.Nature structural & molecular biology · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Structural and Molecular Kinetic Features of Activities of DNA Polymerases.International journal of molecular sciences · 2022
    Review
  20. Structural and functional insight into mismatch extension by human DNA polymerase α.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
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.

Andrey G BaranovskiyFrom the Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, and.
Vincent N Duongthe Departments of Pharmacology and Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06510.
Nigar D BabayevaFrom the Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, and.
Yinbo ZhangFrom the Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, and.
Youri I PavlovFrom the Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, and.
Karen S Andersonthe Departments of Pharmacology and Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06510 karen.anderson@yale.edu.
Tahir H TahirovFrom the Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, and ttahirov@unmc.edu.

Funding

UNMC Structural Biology CoreP20GM103427 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PAUL L SORGEN · 2012 to 2026
$59.2M
UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Joann B. Sweasy · 1985 to 2026
$55.0M
Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
MECHANISM AND INHIBITION OF HIV REVERSE TRANSCRIPTASER01GM049551 · NIGMS · YALE UNIVERSITY · PI ANDERSON, KAREN S. · 1993 to 2019
$9.0M
Predoc Training at the Interface Chemistry and BiologyT32GM067543 · NIGMS · YALE UNIVERSITY · PI CRAWFORD, JASON MICHAEL · 2003 to 2022
$7.4M
UNMC Histology/Imaging and Creighton University Imaging Core FacilityP30GM110768 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI WALSH, EDWARD J · 2014 to 2018
$5.1M
Human DNA Replication Machines: Structure-Function of Polymerase Alpha-PrimaseR01GM101167 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI TAHIROV, TAHIR H · 2013 to 2017
$1.9M
NCI NIH HHS P30 CA036727NIGMS NIH HHS P20 GM103427NIGMS NIH HHS P30 GM110768NIGMS NIH HHS P41 GM103403NIGMS NIH HHS R01 GM049551NIGMS NIH HHS R01 GM101167NIGMS NIH HHS T32 GM067543
6 · The paper itself

Abstract

DNA polymerase α (Polα) plays an important role in genome replication. In a complex with primase, Polα synthesizes chimeric RNA-DNA primers necessary for replication of both chromosomal DNA strands. During RNA primer extension with deoxyribonucleotides, Polα needs to use double-stranded helical substrates having different structures. Here, we provide a detailed structure-function analysis of human Polα's interaction with dNTPs and DNA templates primed with RNA, chimeric RNA-DNA, or DNA. We report the crystal structures of two ternary complexes of the Polα catalytic domain containing dCTP, a DNA template, and either a DNA or an RNA primer. Unexpectedly, in the ternary complex with a DNA:DNA duplex and dCTP, the "fingers" subdomain of Polα is in the open conformation. Polα induces conformational changes in the DNA and hybrid duplexes to produce the universal double helix form. Pre-steady-state kinetic studies indicated for both duplex types that chemical catalysis rather than product release is the rate-limiting step. Moreover, human Polα extended DNA primers with higher efficiency but lower processivity than it did with RNA and chimeric primers. Polα has a substantial propensity to make errors during DNA synthesis, and we observed that its fidelity depends on the type of sugar at the primer 3'-end. A detailed structural comparison of Polα with other replicative DNA polymerases disclosed common features and some differences, which may reflect the specialization of each polymerase in genome replication.

Indexed as

CatalysisCatalytic DomainCations, DivalentCrystallography, X-RayDNA Polymerase IDNA PrimersHumansKineticsMetalsNucleotidesProtein BindingProtein ConformationRNAStructure-Activity RelationshipTemplates, GeneticCations, DivalentDNA Polymerase IDNA PrimersMetalsNucleotidesRNARNA primerschimeric RNA-DNA primerconformational changecrystal structureDNA polymeraseDNA-protein interactionDNA replicationhumanPolαPolδPolεpre-steady-state kineticsRNA

Identifiers

PMID29555682
PMCPMC5936803

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Registered trials

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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.