Evidence map›Paper›PMID 20383123›Full record

ArticleNature2010

Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends.

Steven A Roberts, Natasha Strande, Martin D Burkhalter, Christina Strom, Jody M Havener, Paul Hasty, Dale A Ramsden

Open access · greenAbstract read
In one paragraph

Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
7.7field-weighted citation impact, top 2% 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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.

  1. Pooled it
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  7. Base-excision restriction enzymes: expanding the world of epigenetic immune systems.DNA research : an international journal for rapid publication of reports on genes and genomes · 2023
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62 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 1 country.

Steven A RobertsDepartment of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, and Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Natasha Strande
Martin D Burkhalter
Christina Strom
Jody M Havener
Paul Hasty
Dale A Ramsden
University of North Carolina at Chapel Hill · USThe University of Texas Health Science Center at San Antonio · US

Funding

THE IMPACT OF CELLULAR DEFENSE ON THE ROLE OF Ku80 IN GENOME MAINTENANCE AND LONGP01AG017242 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI VIJG, JAN · 1999 to 2023
$46.1M
Resolution of Complex Breaks by Nonhomologous End JoiningR01CA084442 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAMSDEN, DALE A · 2000 to 2019
$4.8M
XRCC5 MUTANT MICE AND CELL LINESR01CA076317 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI HASTY, EDWARD PAUL · 1997 to 2005
$1.0M
NCI NIH HHS CA 84442NCI NIH HHS R01 CA076317NCI NIH HHS R01 CA084442NCI NIH HHS R01 CA76317-05A1NIA NIH HHS P01 AG017242NIA NIH HHS P01 AG17242
6 · The paper itself

Abstract

Mammalian cells require non-homologous end joining (NHEJ) for the efficient repair of chromosomal DNA double-strand breaks. A key feature of biological sources of strand breaks is associated nucleotide damage, including base loss (abasic or apurinic/apyrimidinic (AP) sites). At single-strand breaks, 5'-terminal abasic sites are excised by the 5'-deoxyribose-5-phosphate (5'-dRP) lyase activity of DNA polymerase beta (pol beta): here we show, in vitro and in cells, that accurate and efficient repair by NHEJ of double-strand breaks with such damage similarly requires 5'-dRP/AP lyase activity. Classically defined NHEJ is moreover uniquely effective at coupling this end-cleaning step to joining in cells, helping to distinguish this pathway from otherwise robust alternative NHEJ pathways. The NHEJ factor Ku can be identified as an effective 5'-dRP/AP lyase. In a similar manner to other lyases, Ku nicks DNA 3' of an abasic site by a mechanism involving a Schiff-base covalent intermediate with the abasic site. We show by using cell extracts that Ku is essential for the efficient removal of AP sites near double-strand breaks and, consistent with this result, that joining of such breaks is specifically decreased in cells complemented with a lyase-attenuated Ku mutant. Ku had previously been presumed only to recognize ends and recruit other factors that process ends; our data support an unexpected direct role for Ku in end-processing steps as well.

Indexed as

BiocatalysisDNA Breaks, Double-StrandedDNA DamageDNA RepairAnimalsAntigens, NuclearCell ExtractsCell LineDNA-(Apurinic or Apyrimidinic Site) LyaseDNA-Binding ProteinsFibroblastsHeLa CellsHumansKu AutoantigenMiceRibosemonophosphates5'-deoxyribose-5-phosphateAntigens, NuclearCell ExtractsDNA-(Apurinic or Apyrimidinic Site) LyaseDNA-Binding ProteinsKu AutoantigenRibosemonophosphatesSchiff BasesXrcc6 protein, humanXrcc6 protein, mouse

Identifiers

PMID20383123
PMCPMC2859099
OpenAlexW2093274002

What OpenQuestion holds

Textmetadata
LicenceTDM
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.