Evidence map›Paper›PMID 18369368›Full record

ArticleEMBO reports2008

Substrate-induced DNA strand misalignment during catalytic cycling by DNA polymerase lambda.

Katarzyna Bebenek, Miguel Garcia-Diaz, Meredith C Foley, Lars C Pedersen, Tamar Schlick, Thomas A Kunkel

Abstract read
In one paragraph

Article in EMBO reports, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed.

  1. Article
  2. Biology and Regulation of Staphylococcal Biofilm.International journal of molecular sciences · 2023
    Review
  3. Article
  4. Article
  5. Article
  6. Structure and function relationships in mammalian DNA polymerases.Cellular and molecular life sciences : CMLS · 2020
    Review
  7. Structural basis for the binding and incorporation of nucleotide analogs with L-stereochemistry by human DNA polymerase λ.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  8. Article
  9. Review
  10. Article
  11. Translesion DNA synthesis and mutagenesis in eukaryotes.Cold Spring Harbor perspectives in biology · 2013
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Replication infidelity via a mismatch with Watson-Crick geometry.Proceedings of the National Academy of Sciences of the United States of America · 2011
    Article
  18. Article
  19. Article
  20. DNA pol λ's extraordinary ability to stabilize misaligned DNA.Journal of the American Chemical Society · 2010
    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

6 authors.

Katarzyna BebenekLaboratory of Structural Biology and Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA.
Miguel Garcia-Diaz
Meredith C Foley
Lars C Pedersen
Tamar Schlick
Thomas A Kunkel

Funding

Structure-Function Studies Of DNA Replication FidelityZ01ES065070 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KUNKEL, THOMAS A · 1991 to 2008
$4.3M
Mechanisms of DNA PolymerasesR01ES012692 · NIEHS · NEW YORK UNIVERSITY · PI SCHLICK, TAMAR · 2005 to 2007
$843k
Intramural NIH HHSNIEHS NIH HHS R01 ES012692
6 · The paper itself

Abstract

The simple deletion of nucleotides is common in many organisms. It can be advantageous when it activates genes beneficial to microbial survival in adverse environments, and deleterious when it mutates genes relevant to survival, cancer or degenerative diseases. The classical idea is that simple deletions arise by strand slippage. A prime opportunity for slippage occurs during DNA synthesis, but it remains unclear how slippage is controlled during a polymerization cycle. Here, we report crystal structures and molecular dynamics simulations of mutant derivatives of DNA polymerase lambda bound to a primer-template during strand slippage. Relative to the primer strand, the template strand is in multiple conformations, indicating intermediates on the pathway to deletion mutagenesis. Consistent with these intermediates, the mutant polymerases generate single-base deletions at high rates. The results indicate that dNTP-induced template strand repositioning during conformational rearrangements in the catalytic cycle is crucial to controlling the rate of strand slippage.

Indexed as

DNA RepairAlanineAmino Acid SubstitutionBinding SitesCatalysisComputer SimulationCrystallography, X-RayDNADNA Polymerase betaGene DeletionHumansHydrogen BondingLysineModels, ChemicalNucleic Acid ConformationTemplates, GeneticAlanineDNADNA Polymerase betaDNA polymerase beta2Lysine

Identifiers

PMID18369368
PMCPMC2278112

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.