Evidence map›Paper›PMID 29950655›Full record

ArticleNature communications2018

C-NHEJ without indels is robust and requires synergistic function of distinct XLF domains.

Ragini Bhargava, Manbir Sandhu, Sanychen Muk, Gabriella Lee, Nagarajan Vaidehi, Jeremy M Stark

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

69 citing papers in PubMed, 105 citations in OpenAlex.

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9 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

6 authors at 2 institutions in 1 country.

Ragini BhargavaDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute of the City of Hope, 1500 E Duarte Rd., Duarte, CA, 91010, USA.
Manbir SandhuIrell and Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, 1500 E Duarte Rd., Duarte, CA, 91010, USA.
Sanychen MukDepartment of Molecular Immunology, Beckman Research Institute of the City of Hope, 1500 E Duarte Rd., Duarte, CA, 91010, USA.ORCID http://orcid.org/0000-0002-3490-8143
Gabriella LeeDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute of the City of Hope, 1500 E Duarte Rd., Duarte, CA, 91010, USA.
Nagarajan VaidehiIrell and Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, 1500 E Duarte Rd., Duarte, CA, 91010, USA.
Jeremy M StarkDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute of the City of Hope, 1500 E Duarte Rd., Duarte, CA, 91010, USA. jstark@coh.org.ORCID http://orcid.org/0000-0002-2625-5373
City of Hope · USCity Of Hope National Medical Center · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
Computationally Guided Design of Thermostable mutants of Neurotensin receptor1R01GM097261 · NIGMS · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI VAIDEHI, NAGARAJAN · 2011 to 2018
$2.3M
Mechanistic steps of homologous repair in mammalian cellsR01CA120954 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI STARK, JEREMY MICHAEL · 2006 to 2016
$2.2M
Regulation of Single Strand Annealing Repair of Mammalian Chromosomal BreaksR01CA197506 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI STARK, JEREMY MICHAEL · 2016 to 2020
$1.9M
NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA120954NCI NIH HHS R01 CA197506NIGMS NIH HHS R01 GM097261
6 · The paper itself

Abstract

To investigate the fidelity of canonical non-homologous end joining (C-NHEJ), we developed an assay to detect EJ between distal ends of two Cas9-induced chromosomal breaks that are joined without causing insertion/deletion mutations (indels). Here we find that such EJ requires several core C-NHEJ factors, including XLF. Using variants of this assay, we find that C-NHEJ is required for EJ events that use 1-2, but not ≥3, nucleotides of terminal microhomology. We also investigated XLF residues required for EJ without indels, finding that one of two binding domains is essential (L115 or C-terminal lysines that bind XRCC4 and KU/DNA, respectively), and that disruption of one of these domains sensitizes XLF to mutations that affect its dimer interface, which we examined with molecular dynamic simulations. Thus, C-NHEJ, including synergistic function of distinct XLF domains, is required for EJ of chromosomal breaks without indels.

Indexed as

Chromosome BreakageDNA End-Joining RepairAnimalsCell LineDNA-Binding ProteinsFibroblastsINDEL MutationKu AutoantigenMiceMolecular Dynamics SimulationMouse Embryonic Stem CellsProtein BindingProtein DomainsProtein MultimerizationDNA-Binding ProteinsKu AutoantigenXLF protein, mouseXRCC4 protein, mouseXrcc6 protein, mouse

Identifiers

PMID29950655
PMCPMC6021437
OpenAlexW2809529383

What OpenQuestion holds

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LicenceCC BY
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.