Evidence map›Paper›PMID 30583959›Full record

ArticleDNA repair2019

Repair of protein-linked DNA double strand breaks: Using the adenovirus genome as a model substrate in cell-based assays.

Brandon J Lamarche, Nicole I Orazio, Brittany Goben, Jill Meisenhelder, Zhongsheng You, Matthew D Weitzman, Tony Hunter

Open access · greenAbstract read
In one paragraph

Article in DNA repair, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
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.

Brandon J LamarcheLaboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, 92037, USA; Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, 92037, USA.
Nicole I OrazioLaboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, 92037, USA.
Brittany GobenMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, 92037, USA.
Jill MeisenhelderMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, 92037, USA.
Zhongsheng YouDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Matthew D WeitzmanLaboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, 92037, USA. Electronic address: weitzmanm@email.chop.edu.
Tony HunterMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, 92037, USA. Electronic address: hunter@salk.edu.
Salk Institute for Biological Studies · USWashington University in St. Louis · US

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8M
Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
SOMATIC CELL CYCLE REGULATION BY PHOSPHORYLATIONR01CA080100 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HUNTER, TONY R. · 1999 to 2018
$13.1M
SIGNAL TRANSDUCTION BY TYROSINE PHOSPHORYLATIONR01CA082683 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HUNTER, TONY R. · 1999 to 2019
$12.2M
Contemporary Approaches to Cancer Cell Signaling and CommunicationT32CA009523 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DONOGHUE, DANIEL J, YANG, JING · 1985 to 2025
$12.1M
Viral Modulation of Genetic StabilityR01CA097093 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI WEITZMAN, MATTHEW D. · 2003 to 2019
$5.2M
AAV and the DNA Damage MachineryR01AI067952 · NIAID · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI WEITZMAN, MATTHEW D. · 2006 to 2010
$2.1M
Regulation of Receptor Tyrosine KinasesR01GM065490 · NIGMS · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI DONOGHUE, DANIEL J · 2002 to 2005
$1.0M
Identifying proteins involved in virus DNA replicationR21AI115104 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI WEITZMAN, MATTHEW D. · 2016 to 2017
$462k
NCI NIH HHS P01 CA120964NCI NIH HHS P30 CA014195NCI NIH HHS R01 CA080100NCI NIH HHS R01 CA082683NCI NIH HHS R01 CA097093NCI NIH HHS T32 CA009523NIAID NIH HHS R01 AI067952NIAID NIH HHS R21 AI115104NIGMS NIH HHS R01 GM065490
6 · The paper itself

Abstract

The DNA double strand breaks (DSBs) created during meiotic recombination and during some types of chemotherapy contain protein covalently attached to their 5' termini. Removal of the end-blocking protein is a prerequisite to DSB processing by non-homologous end-joining or homologous recombination. One mechanism for removing the protein involves CtIP-stimulated Mre11-catalyzed nicking of the protein-linked strand distal to the DSB terminus, releasing the end-blocking protein while it remains covalently attached to an oligonucleotide. Much of what is known about this repair process has recently been deciphered through in vitro reconstitution studies. We present here a novel model system based on adenovirus (Ad), which contains the Ad terminal protein covalently linked to the 5' terminus of its dsDNA genome, for studying the repair of 5' protein-linked DSBs in vivo. It was previously shown that the genome of Ad mutants that lack early region 4 (E4) can be joined into concatemers in vivo, suggesting that the Ad terminal protein had been removed from the genome termini prior to ligation. Here we show that during infection with the E4-deleted Ad mutant dl1004, the Ad terminal protein is removed in a manner that recapitulates removal of end-blocking proteins from cellular DSBs. In addition to displaying a dependence on CtIP, and Mre11 acting as the endonuclease, the protein-linked oligonucleotides that are released from the viral genome are similar in size to the oligos that remain attached to Spo11 and Top2 after they are removed from the 5' termini of DSBs during meiotic recombination and etoposide chemotherapy, respectively. The single nucleotide resolution that is possible with this assay, combined with the single sequence context in which the lesion is presented, make it a useful tool for further refining our mechanistic understanding of how blocking proteins are removed from the 5' termini of DSBs.

Indexed as

DNA Breaks, Double-StrandedDNA RepairAdenoviridaeBRCA1 ProteinCarrier ProteinsEndodeoxyribonucleasesGene Knockdown TechniquesGenome, ViralHEK293 CellsHumansMRE11 Homologue ProteinNuclear ProteinsProteinsBRCA1 ProteinCarrier ProteinsEndodeoxyribonucleasesMRE11 Homologue ProteinMRE11 protein, humanNuclear ProteinsProteinsRBBP8 protein, humanAdenovirusChemotherapyConcatemerCtIPdl1004DNA double strand breakEnd blockingEndonucleaseEnd processingEtoposideHomologous recombinationLigationMre11MRNNonhomologous end joiningProtein-DNA adductProtein-linked DSBSpo11Terminal proteinTopoisomerase 2

Identifiers

PMID30583959
PMCPMC8057058
OpenAlexW2904277373

What OpenQuestion holds

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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.