Evidence map›Paper›PMID 36477609›Full record

ArticleNucleic acids research2023

A scanning-to-incision switch in TFIIH-XPG induced by DNA damage licenses nucleotide excision repair.

Amer Bralić, Muhammad Tehseen, Mohamed A Sobhy, Chi-Lin Tsai, Lubna Alhudhali, Gang Yi, Jina Yu, Chunli Yan, Ivaylo Ivanov, Susan E Tsutakawa and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 31 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

12 authors at 4 institutions in 2 countries.

Amer BralićBioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Muhammad TehseenBioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Mohamed A SobhyBioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Chi-Lin TsaiDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Lubna AlhudhaliBioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Gang YiBioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Jina YuDepartment of Chemistry, Georgia State University, Atlanta, GA 30302 USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30302, USA.
Chunli YanDepartment of Chemistry, Georgia State University, Atlanta, GA 30302 USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30302, USA.
Ivaylo IvanovDepartment of Chemistry, Georgia State University, Atlanta, GA 30302 USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30302, USA.ORCID 0000-0002-5306-1005
Susan E TsutakawaMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
John A TainerMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.ORCID 0000-0003-1659-2429
Samir M HamdanBioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.ORCID 0000-0001-5192-1852
King Abdullah University of Science and Technology · SAGeorgia State University · USThe University of Texas MD Anderson Cancer Center · USLawrence Berkeley National Laboratory · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI WALTER J. CHAZIN · 2001 to 2026
$89.6M
Mesoscale and Nanoscale Technologies Integrated by Structures for DNA Repair Complexes (MANTIS-DRC)R35CA220430 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI John A. Tainer · 2018 to 2026
$7.6M
Integrative Modeling of Biomolecular Machinery in Nucleotide Excision RepairR01ES032786 · NIEHS · GEORGIA STATE UNIVERSITY · PI Ivaylo Nikolaev Ivanov · 2022 to 2026
$1.7M
NCI NIH HHS R35 CA220430
6 · The paper itself

Abstract

Nucleotide excision repair (NER) is critical for removing bulky DNA base lesions and avoiding diseases. NER couples lesion recognition by XPC to strand separation by XPB and XPD ATPases, followed by lesion excision by XPF and XPG nucleases. Here, we describe key regulatory mechanisms and roles of XPG for and beyond its cleavage activity. Strikingly, by combing single-molecule imaging and bulk cleavage assays, we found that XPG binding to the 7-subunit TFIIH core (coreTFIIH) stimulates coreTFIIH-dependent double-strand (ds)DNA unwinding 10-fold, and XPG-dependent DNA cleavage by up to 700-fold. Simultaneous monitoring of rates for coreTFIIH single-stranded (ss)DNA translocation and dsDNA unwinding showed XPG acts by switching ssDNA translocation to dsDNA unwinding as a likely committed step. Pertinent to the NER pathway regulation, XPG incision activity is suppressed during coreTFIIH translocation on DNA but is licensed when coreTFIIH stalls at the lesion or when ATP hydrolysis is blocked. Moreover, ≥15 nucleotides of 5'-ssDNA is a prerequisite for efficient translocation and incision. Our results unveil a paired coordination mechanism in which key lesion scanning and DNA incision steps are sequentially coordinated, and damaged patch removal is only licensed after generation of ≥15 nucleotides of 5'-ssDNA, ensuring the correct ssDNA bubble size before cleavage.

Indexed as

DNA RepairTranscription Factor TFIIHDNADNA DamageDNA, Single-StrandedEndonucleasesNucleotidesDNADNA, Single-StrandedEndonucleasesNucleotidesTranscription Factor TFIIH

Identifiers

PMID36477609
PMCPMC9943652
OpenAlexW4310940015

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.