Evidence map›Paper›PMID 30213916›Full record

ArticleScience (New York, N.Y.)2018

Ribonucleotide incorporation enables repair of chromosome breaks by nonhomologous end joining.

John M Pryor, Michael P Conlin, Juan Carvajal-Garcia, Megan E Luedeman, Adam J Luthman, George W Small, Dale A Ramsden

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

55 citing papers in PubMed, 97 citations in OpenAlex.

  1. RNASEH2B loss and PARP inhibition in advanced prostate cancer.The Journal of clinical investigation · 2024
    Trial
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  19. How RNA impacts DNA repair.DNA repair · 2023
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

John M PryorLineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.ORCID 0000-0001-7000-9383
Michael P ConlinLineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.ORCID 0000-0001-6555-3624
Juan Carvajal-GarciaLineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.ORCID 0000-0001-7257-3674
Megan E LuedemanLineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.ORCID 0000-0003-3616-0770
Adam J LuthmanLineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.ORCID 0000-0001-6695-880X
George W SmallLineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.ORCID 0000-0002-7585-7258
Dale A RamsdenLineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA. dale_ramsden@med.unc.edu.ORCID 0000-0003-1575-4748
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
NRSA IN GENETICST32GM007092 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEKELSKY, JEFF J. · 1985 to 2019
$5.9M
The Role of DNA Synthesis in Nonhomologous End JoiningR01CA097096 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DALE A RAMSDEN · 2003 to 2026
$5.5M
DNA Polymerases in Nonhomologous End JoiningU01CA097096 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAMSDEN, DALE A · 2019 to 2022
$1.4M
Training in Mechanistic, Interdisciplinary Studies of Biological SystemsT32GM119999 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAMSDEN, DALE A · 2017 to 2021
$1.2M
Mechanism of Damage Tolerance by Nonhomologous End JoiningF31CA203156 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CONLIN, MICHAEL PATRICK · 2017 to 2018
$41k
NCI NIH HHS F31 CA203156NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA097096NCI NIH HHS U01 CA097096NIGMS NIH HHS T32 GM119999
6 · The paper itself

Abstract

The nonhomologous end-joining (NHEJ) pathway preserves genome stability by ligating the ends of broken chromosomes together. It employs end-processing enzymes, including polymerases, to prepare ends for ligation. We show that two such polymerases incorporate primarily ribonucleotides during NHEJ-an exception to the central dogma of molecular biology-both during repair of chromosome breaks made by Cas9 and during V(D)J recombination. Moreover, additions of ribonucleotides but not deoxynucleotides effectively promote ligation. Repair kinetics suggest that ribonucleotide-dependent first-strand ligation is followed by complementary strand repair with deoxynucleotides, then by replacement of ribonucleotides embedded in the first strand with deoxynucleotides. Our results indicate that as much as 65% of cellular NHEJ products have transiently embedded ribonucleotides, which promote flexibility in repair at the cost of more fragile intermediates.

Indexed as

Chromosome BreakageDNA End-Joining RepairDNA RepairAnimalsBacterial ProteinsCell LineClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9DNA-Directed DNA PolymeraseEndonucleasesEosinophil-Derived NeurotoxinFibroblastsGenomic InstabilityMiceRibonucleotidesV(D)J RecombinationBacterial ProteinsCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9DNA-Directed DNA PolymeraseEar2 protein, mouseEndonucleasesEosinophil-Derived NeurotoxinPolm protein, mouseRibonucleotides

Identifiers

PMID30213916
PMCPMC6252249
OpenAlexW2891034002

What OpenQuestion holds

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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.