Evidence map›Paper›PMID 22362780›Full record

ArticleThe Journal of biological chemistry2012

Specificity of the dRP/AP lyase of Ku promotes nonhomologous end joining (NHEJ) fidelity at damaged ends.

Natasha Strande, Steven A Roberts, Sehyun Oh, Eric A Hendrickson, Dale A Ramsden

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
–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

34 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
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  7. Article
  8. The Multifaceted Roles of Ku70/80.International journal of molecular sciences · 2021
    Review
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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

5 authors.

Natasha StrandeLineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Steven A Roberts
Sehyun Oh
Eric A Hendrickson
Dale A Ramsden

Funding

Resolution of Complex Breaks by Nonhomologous End JoiningR01CA084442 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAMSDEN, DALE A · 2000 to 2019
$4.8M
The mechanism of Cas9/CRISPR-initiated genome modification in human somatic cellsR01GM088351 · NIGMS · UNIVERSITY OF MINNESOTA · PI HENDRICKSON, ERIC A · 2010 to 2018
$2.3M
Ku regulates non-homologous end joining pathways in human somatic cellsR01CA154461 · NCI · UNIVERSITY OF MINNESOTA · PI HENDRICKSON, ERIC A · 2011 to 2015
$1.6M
NCI NIH HHS R01 CA084442NCI NIH HHS R01 CA154461NCI NIH HHS R01 CA 84442NIGMS NIH HHS R01 GM088351
6 · The paper itself

Abstract

Nonhomologous end joining (NHEJ) is essential for efficient repair of chromosome breaks. However, the NHEJ ligation step is often obstructed by break-associated nucleotide damage, including base loss (abasic site or 5'-dRP/AP sites). Ku, a 5'-dRP/AP lyase, can excise such damage at ends in preparation for the ligation step. We show here that this activity is greatest if the abasic site is within a short 5' overhang, when this activity is necessary and sufficient to prepare such termini for ligation. In contrast, Ku is less active near 3' strand termini, where excision would leave a ligation-blocking α,β-unsaturated aldehyde. The Ku AP lyase activity is also strongly suppressed by as little as two paired bases 5' of the abasic site. Importantly, in vitro end joining experiments show that abasic sites significantly embedded in double-stranded DNA do not block the NHEJ ligation step. Suppression of the excision activity of Ku in this context therefore is not essential for ligation and further helps NHEJ retain terminal sequence in junctions. We show that the DNA between the 5' terminus and the abasic site can also be retained in junctions formed by cellular NHEJ, indicating that these sites are at least partly resistant to other abasic site-cleaving activities as well. High levels of the 5'-dRP/AP lyase activity of Ku are thus restricted to substrates where excision of an abasic site is required for ligation, a degree of specificity that promotes more accurate joining.

Indexed as

DNA End-Joining RepairBinding SitesCell LineDNADNA-(Apurinic or Apyrimidinic Site) LyaseDNA DamageDNA HelicasesDNA RepairHumansKu AutoantigenOligonucleotidesProteinsProtein Structure, TertiaryRecombinant ProteinsRecombination, GeneticSubstrate SpecificityDNADNA-(Apurinic or Apyrimidinic Site) LyaseDNA HelicasesKu AutoantigenOligonucleotidesProteinsRecombinant ProteinsXRCC5 protein, human

Identifiers

PMID22362780
PMCPMC3340204

What OpenQuestion holds

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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.