Evidence map›Paper›PMID 28109743›Full record

ArticleDNA repair2017

Regulation of human polλ by ATM-mediated phosphorylation during non-homologous end joining.

Guillermo Sastre-Moreno, John M Pryor, Marta Moreno-Oñate, Andrés M Herrero-Ruiz, Felipe Cortés-Ledesma, Luis Blanco, Dale A Ramsden, Jose F Ruiz

Open access · hybridAbstract read
In one paragraph

Article in DNA repair, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

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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

8 authors at 4 institutions in 2 countries.

Guillermo Sastre-MorenoCentro de Biología Molecular "Severo Ochoa", Universidad Autónoma de Madrid/CSIC, Madrid 28049, Spain.
John M PryorDepartment of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Marta Moreno-OñateDepartamento Bioquímica Vegetal y Biología Molecular, Universidad de Sevilla, Sevilla 41092, Spain; Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla/CSIC, Sevilla 41092, Spain.
Andrés M Herrero-RuizCentro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla/CSIC, Sevilla 41092, Spain.
Felipe Cortés-LedesmaCentro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla/CSIC, Sevilla 41092, Spain.
Luis BlancoCentro de Biología Molecular "Severo Ochoa", Universidad Autónoma de Madrid/CSIC, Madrid 28049, Spain.
Dale A RamsdenDepartment of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Jose F RuizDepartamento Bioquímica Vegetal y Biología Molecular, Universidad de Sevilla, Sevilla 41092, Spain; Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla/CSIC, Sevilla 41092, Spain. Electronic address: jose.ruiz@cabimer.es.
Universidad de Sevilla · ESCentro de Biología Molecular Severo Ochoa · ESUNC Lineberger Comprehensive Cancer CenterCentro Andaluz de Biología Molecular y Medicina Regenerativa · ES

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
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
NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA097096NCI NIH HHS U01 CA097096
6 · The paper itself

Abstract

DNA double strand breaks (DSBs) trigger a variety of cellular signaling processes, collectively termed the DNA-damage response (DDR), that are primarily regulated by protein kinase ataxia-telangiectasia mutated (ATM). Among DDR activated processes, the repair of DSBs by non-homologous end joining (NHEJ) is essential. The proper coordination of NHEJ factors is mainly achieved through phosphorylation by an ATM-related kinase, the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), although the molecular basis for this regulation has yet to be fully elucidated. In this study we identify the major NHEJ DNA polymerase, DNA polymerase lambda (Polλ), as a target for both ATM and DNA-PKcs in human cells. We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ. Molecular evidence suggests that Polλ phosphorylation might favor Polλ interaction with the DNA-PK complex at DSBs. Altogether, our work provides the first demonstration of how Polλ is regulated by phosphorylation to connect with the NHEJ core machinery during DSB repair in human cells.

Indexed as

DNA End-Joining RepairAmino Acid SequenceAtaxia Telangiectasia Mutated ProteinsDNA-Activated Protein KinaseDNA Breaks, Double-StrandedDNA Polymerase betaEnzyme ActivationHumansNuclear ProteinsPhosphorylationSequence AlignmentAtaxia Telangiectasia Mutated ProteinsATM protein, humanDNA-Activated Protein KinaseDNA Polymerase betaDNA polymerase beta2Nuclear ProteinsPRKDC protein, human

Identifiers

PMID28109743
PMCPMC5444907
OpenAlexW2573767984

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.