Evidence map›Paper›PMID 20961817›Full record

ArticleDNA repair2011

Efficiency and fidelity of human DNA polymerases λ and β during gap-filling DNA synthesis.

Jessica A Brown, Lindsey R Pack, Laura E Sanman, Zucai Suo

Abstract read
In one paragraph

Article in DNA repair, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

28 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Disentangling sources of clock-like mutations in germline and soma.bioRxiv : the preprint server for biology · 2023
    Article
  8. Interlocking activities of DNA polymerase β in the base excision repair pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Review
  10. Article
  11. Strand Displacement Activity of PrimPol.International journal of molecular sciences · 2020
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Creative template-dependent synthesis by human polymerase mu.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  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 at 1 institution in 1 country.

Jessica A BrownDepartment of Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Lindsey R Pack
Laura E Sanman
Zucai Suo
The Ohio State University · US

Funding

Mechanistic and Structure-Function Studies of Human DNA Polymerase LambdaR01GM079403 · NIGMS · OHIO STATE UNIVERSITY · PI SUO, ZUCAI · 2007 to 2011
$1.7M
NIGMS NIH HHS GM079403NIGMS NIH HHS R01 GM079403
6 · The paper itself

Abstract

The base excision repair (BER) pathway coordinates the replacement of 1-10 nucleotides at sites of single-base lesions. This process generates DNA substrates with various gap sizes which can alter the catalytic efficiency and fidelity of a DNA polymerase during gap-filling DNA synthesis. Here, we quantitatively determined the substrate specificity and base substitution fidelity of human DNA polymerase λ (Pol λ), an enzyme proposed to support the known BER DNA polymerase β (Pol β), as it filled 1-10-nucleotide gaps at 1-nucleotide intervals. Pol λ incorporated a correct nucleotide with relatively high efficiency until the gap size exceeded 9 nucleotides. Unlike Pol λ, Pol β did not have an absolute threshold on gap size as the catalytic efficiency for a correct dNTP gradually decreased as the gap size increased from 2 to 10 nucleotides and then recovered for non-gapped DNA. Surprisingly, an increase in gap size resulted in lower polymerase fidelity for Pol λ, and this downregulation of fidelity was controlled by its non-enzymatic N-terminal domains. Overall, Pol λ was up to 160-fold more error-prone than Pol β, thereby suggesting Pol λ would be more mutagenic during long gap-filling DNA synthesis. In addition, dCTP was the preferred misincorporation for Pol λ and its N-terminal domain truncation mutants. This nucleotide preference was shown to be dependent upon the identity of the adjacent 5'-template base. Our results suggested that both Pol λ and Pol β would catalyze nucleotide incorporation with the highest combination of efficiency and accuracy when the DNA substrate contains a single-nucleotide gap. Thus, Pol λ, like Pol β, is better suited to catalyze gap-filling DNA synthesis during short-patch BER in vivo, although, Pol λ may play a role in long-patch BER.

Indexed as

DNA RepairAmino Acid MotifsBase SequenceDeoxyribonucleotidesDNADNA Polymerase betaHumansKineticsMutationSubstrate SpecificityDeoxyribonucleotidesDNADNA Polymerase betaDNA polymerase beta2

Identifiers

PMID20961817
PMCPMC3065367
OpenAlexW2092562445

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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.