Evidence map›Paper›PMID 34428697›Full record

ArticleDNA repair2021

Impact of DNA sequences on DNA 'opening' by the Rad4/XPC nucleotide excision repair complex.

Debamita Paul, Hong Mu, Amirrasoul Tavakoli, Qing Dai, Sagnik Chakraborty, Chuan He, Anjum Ansari, Suse Broyde, Jung-Hyun Min

Open access · greenAbstract read
In one paragraph

Article in DNA repair, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

5 citing papers in PubMed, 11 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

9 authors at 5 institutions in 1 country.

Debamita PaulDepartment of Chemistry and Biochemistry, Baylor University, Waco, TX, 76798, USA.
Hong MuDepartment of Biology, New York University, New York, NY, 10003, USA.
Amirrasoul TavakoliDepartment of Chemistry and Biochemistry, Baylor University, Waco, TX, 76798, USA.
Qing DaiDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Sagnik ChakrabortyDepartment of Physics, University of Illinois at Chicago, Chicago, IL, 60607, USA.
Chuan HeDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA; Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, 60637, USA.
Anjum AnsariDepartment of Physics, University of Illinois at Chicago, Chicago, IL, 60607, USA.
Suse BroydeDepartment of Biology, New York University, New York, NY, 10003, USA. Electronic address: broyde@nyu.edu.
Jung-Hyun MinDepartment of Chemistry and Biochemistry, Baylor University, Waco, TX, 76798, USA. Electronic address: JungHyun_Min@baylor.edu.
Baylor University · USNew York University · USUniversity of Illinois Chicago · USHoward Hughes Medical Institute · USUniversity of Chicago · US

Funding

Labeling and sequencing of 5hmC and 5mC in DNA-RenewalR01HG006827 · NHGRI · UNIVERSITY OF CHICAGO · PI HE, CHUAN · 2012 to 2025
$7.2M
Environmental DNA Lesions and Mutagenesis: Molecular Mechanisms of Lesion Recognition for Repair and Polymerase BypassR01ES025987 · NIEHS · NEW YORK UNIVERSITY · PI BROYDE, SUSE · 2016 to 2025
$3.6M
Arylamine DNA adduct recognition in eukaryotic nucleotide excision repairR21ES028384 · NIEHS · UNIVERSITY OF RHODE ISLAND · PI CHO, BONGSUP P, MIN, JUNG-HYUN · 2017 to 2018
$443k
Howard Hughes Medical InstituteNHGRI NIH HHS R01 HG006827NIEHS NIH HHS R01 ES025987NIEHS NIH HHS R21 ES028384
6 · The paper itself

Abstract

Rad4/XPC recognizes diverse DNA lesions to initiate nucleotide excision repair (NER). However, NER propensities among lesions vary widely and repair-resistant lesions are persistent and thus highly mutagenic. Rad4 recognizes repair-proficient lesions by unwinding ('opening') the damaged DNA site. Such 'opening' is also observed on a normal DNA sequence containing consecutive C/G's (CCC/GGG) when tethered to Rad4 to prevent protein diffusion. However, it was unknown if such tethering-facilitated DNA 'opening' could occur on any DNA or if certain structures/sequences would resist being 'opened'. Here, we report that DNA containing alternating C/G's (CGC/GCG) failed to be opened even when tethered; instead, Rad4 bound in a 180°-reversed manner, capping the DNA end. Fluorescence lifetime studies of DNA conformations in solution showed that CCC/GGG exhibits local pre-melting that is absent in CGC/GCG. In MD simulations, CGC/GCG failed to engage Rad4 to promote 'opening' contrary to CCC/GGG. Altogether, our study illustrates how local sequences can impact DNA recognition by Rad4/XPC and how certain DNA sites resist being 'opened' even with Rad4 held at that site indefinitely. The contrast between CCC/GGG and CGC/GCG sequences in Rad4-DNA recognition may help decipher a lesion's mutagenicity in various genomic sequence contexts to explain lesion-determined mutational hot and cold spots.

Indexed as

DNA RepairSaccharomyces cerevisiae ProteinsBase SequenceDNADNA-Binding ProteinsDNA DamageMolecular Dynamics SimulationNucleic Acid ConformationProtein BindingSaccharomyces cerevisiaeDNADNA-Binding ProteinsRad4 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsDNA damage recognitionFluorescence lifetimeFörster resonance energy transferMolecular dynamics simulationNucleotide excision repairProtein-DNA interactionRad4Sequence impactTime-resolved fluorescenceXeroderma pigmentosumXPCx-ray crystallography

Identifiers

PMID34428697
PMCPMC8934541
OpenAlexW3190261505

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.