Evidence map›Paper›PMID 22021378›Full record

ArticleNucleic acids research2012

Beyond translesion synthesis: polymerase κ fidelity as a potential determinant of microsatellite stability.

Suzanne E Hile, Xiaoxiao Wang, Marietta Y W T Lee, Kristin A Eckert

Abstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Creation and resolution of non-B-DNA structural impediments during replication.Critical reviews in biochemistry and molecular biology · 2022
    Article
  5. RIP140 regulatesCancer drug resistance (Alhambra, Calif.) · 2022
    Article
  6. Article
  7. Mammalian DNA Polymerase Kappa Activity and Specificity.Molecules (Basel, Switzerland) · 2019
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

4 authors.

Suzanne E HileDepartment of Pathology, Gittlen Cancer Research Foundation, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Xiaoxiao Wang
Marietta Y W T Lee
Kristin A Eckert

Funding

BIOCHEMICAL STUDIES OF POLYMERASE DELTAR01GM031973 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LEE, MARIETTA Y. · 1985 to 2012
$5.8M
Modification of DNA Polymerase Delta by a Novel Mechanism During Replication StreR01ES014737 · NIEHS · NEW YORK MEDICAL COLLEGE · PI LEE, MARIETTA Y., ZHANG, ZHONGTAO · 2008 to 2017
$3.5M
Computational and Biochemical Analysis of Microsatellite Life CycleR01GM087472 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI ECKERT, KRISTIN A, MAKOVA, KATERYNA · 2009 to 2012
$1.4M
DNA replication, DNA repair and microsatellite stabilityR01CA100060 · NCI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI ECKERT, KRISTIN A · 2005 to 2009
$1.3M
NCI NIH HHS CA100060NIEHS NIH HHS ES014737NIGMS NIH HHS GM31973NIGMS NIH HHS GM87472NIGMS NIH HHS R01 GM031973
6 · The paper itself

Abstract

Microsatellite DNA synthesis represents a significant component of human genome replication that must occur faithfully. However, yeast replicative DNA polymerases do not possess high fidelity for microsatellite synthesis. We hypothesized that the structural features of Y-family polymerases that facilitate accurate translesion synthesis may promote accurate microsatellite synthesis. We compared human polymerases κ (Pol κ) and η (Pol η) fidelities to that of replicative human polymerase δ holoenzyme (Pol δ4), using the in vitro HSV-tk assay. Relative polymerase accuracy for insertion/deletion (indel) errors within 2-3 unit repeats internal to the HSV-tk gene concurred with the literature: Pol δ4 >> Pol κ or Pol η. In contrast, relative polymerase accuracy for unit-based indel errors within [GT](10) and [TC](11) microsatellites was: Pol κ ≥ Pol δ4 > Pol η. The magnitude of difference was greatest between Pols κ and δ4 with the [GT] template. Biochemically, Pol κ displayed less synthesis termination within the [GT] allele than did Pol δ4. In dual polymerase reactions, Pol κ competed with either a stalled or moving Pol δ4, thereby reducing termination. Our results challenge the ideology that pol κ is error prone, and suggest that DNA polymerases with complementary biochemical properties can function cooperatively at repetitive sequences.

Indexed as

Microsatellite InstabilityMicrosatellite RepeatsAllelesDNADNA DamageDNA-Directed DNA PolymeraseDNA Polymerase IIIHumansINDEL MutationY-Family DNA PolymerasesDNADNA-Directed DNA PolymeraseDNA Polymerase IIIPOLK protein, humanRad30 proteinY-Family DNA Polymerases

Identifiers

PMID22021378
PMCPMC3287198

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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.