Evidence map›Paper›PMID 23558743›Full record

ArticleNucleic acids research2013

Human polymerase kappa uses a template-slippage deletion mechanism, but can realign the slipped strands to favour base substitution mutations over deletions.

Purba Mukherjee, Indrajit Lahiri, Janice D Pata

Abstract read
In one paragraph

Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Revisiting mutagenesis at non-B DNA motifs in the human genome.Nature structural & molecular biology · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  13. Review
  14. Article
  15. Review
  16. 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

3 authors.

Purba MukherjeeWadsworth Center, New York State Department of Health, University at Albany, School of Public Health, Albany, NY 12201-0509, USA.
Indrajit Lahiri
Janice D Pata

Funding

Structural and Mechanistic Studies of Error-Prone PolymerasesR01GM080573 · NIGMS · WADSWORTH CENTER · PI PATA, JANICE D · 2008 to 2018
$2.6M
NIGMS NIH HHS GM080573NIGMS NIH HHS R01 GM080573
6 · The paper itself

Abstract

Polymerases belonging to the DinB class of the Y-family translesion synthesis DNA polymerases have a preference for accurately and efficiently bypassing damaged guanosines. These DinB polymerases also generate single-base (-1) deletions at high frequencies with most occurring on repetitive 'deletion hotspot' sequences. Human DNA polymerase kappa (hPolκ), the eukaryotic DinB homologue, displays an unusual efficiency for to extend from mispaired primer termini, either by extending directly from the mispair or by primer-template misalignment. This latter property explains how hPolκ creates single-base deletions in non-repetitive sequences, but does not address how deletions occur in repetitive deletion hotspots. Here, we show that hPolκ uses a classical Streisinger template-slippage mechanism to generate -1 deletions in repetitive sequences, as do the bacterial and archaeal homologues. After the first nucleotide is added by template slippage, however, hPolκ can efficiently realign the primer-template duplex before continuing DNA synthesis. Strand realignment results in a base-substitution mutation, minimizing generation of more deleterious frameshift mutations. On non-repetitive sequences, we find that nucleotide misincorporation is slower if the incoming nucleotide can correctly basepair with the nucleotide immediately 5' to the templating base, thereby competing against the mispairing with the templating base.

Indexed as

MutationBase SequenceDeoxycytosine NucleotidesDNADNA-Directed DNA PolymeraseHumansNucleotidesRepetitive Sequences, Nucleic AcidTemplates, GeneticY-Family DNA Polymerases2'-deoxycytidine 5'-triphosphateDeoxycytosine NucleotidesDNADNA-Directed DNA PolymeraseNucleotidesPOLK protein, humanY-Family DNA Polymerases

Identifiers

PMID23558743
PMCPMC3643592

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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.