Evidence map›Paper›PMID 22859295›Full record

ArticleThe Journal of biological chemistry2012

Structural basis of Rev1-mediated assembly of a quaternary vertebrate translesion polymerase complex consisting of Rev1, heterodimeric polymerase (Pol) ζ, and Pol κ.

Jessica Wojtaszek, Chul-Jin Lee, Sanjay D'Souza, Brenda Minesinger, Hyungjin Kim, Alan D D'Andrea, Graham C Walker, Pei Zhou

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

85 citing papers in PubMed, 113 citations in OpenAlex.

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  5. Sensitization of cancer cells to DNA-damaging agents by expression of the REV1 C-terminal domain: Implications for chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2025
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25 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

8 authors at 3 institutions in 1 country.

Jessica WojtaszekDepartment of Biochemistry, Duke University, Medical Center, Durham, North Carolina 27710, USA.
Chul-Jin Lee
Sanjay D'Souza
Brenda Minesinger
Hyungjin Kim
Alan D D'Andrea
Graham C Walker
Pei Zhou
Duke University · USMassachusetts Institute of Technology · USDana-Farber Cancer Institute · US

Funding

STRUCTURE AND FUNCTION OF THE ERYTHROPOIETIN RECEPTORR01DK043889 · NIDDK · DANA-FARBER CANCER INSTITUTE · PI D'ANDREA, ALAN D. · 1992 to 2014
$5.3M
Molecular Pathogenesis of Fanconi AnemiaR37HL052725 · NHLBI · DANA-FARBER CANCER INSTITUTE · PI D'ANDREA, ALAN D. · 2004 to 2013
$3.9M
Novel therapies for Fanconi anemiaRC4DK090913 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI D'ANDREA, ALAN D., DALEY, GEORGE Q · 2010 to 2010
$3.9M
Mechanism of Eukaryotic Environmental MutagenesisR01ES015818 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WALKER, GRAHAM C · 2007 to 2016
$3.8M
Structural, Biochemical and Functional Studies of RNAPII CTD Interacting ProteinsR01GM079376 · NIGMS · DUKE UNIVERSITY · PI ZHOU, PEI · 2008 to 2011
$1.2M
Mechanism of Eukaryotic Environmental MutagenesisR56ES015818 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WALKER, GRAHAM C · 2011 to 2011
$200k
NHLBI NIH HHS R37 HL052725NHLBI NIH HHS R37HL52725NIDDK NIH HHS R01 DK043889NIDDK NIH HHS R01DK43889NIDDK NIH HHS RC4 DK090913NIDDK NIH HHS RC4DK090913NIEHS NIH HHS ES-015818NIEHS NIH HHS R01 ES015818NIEHS NIH HHS R56 ES015818NIGMS NIH HHS GM-079376NIGMS NIH HHS R01 GM079376
6 · The paper itself

Abstract

DNA synthesis across lesions during genomic replication requires concerted actions of specialized DNA polymerases in a potentially mutagenic process known as translesion synthesis. Current models suggest that translesion synthesis in mammalian cells is achieved in two sequential steps, with a Y-family DNA polymerase (κ, η, ι, or Rev1) inserting a nucleotide opposite the lesion and with the heterodimeric B-family polymerase ζ, consisting of the catalytic Rev3 subunit and the accessory Rev7 subunit, replacing the insertion polymerase to carry out primer extension past the lesion. Effective translesion synthesis in vertebrates requires the scaffolding function of the C-terminal domain (CTD) of Rev1 that interacts with the Rev1-interacting region of polymerases κ, η, and ι and with the Rev7 subunit of polymerase ζ. We report the purification and structure determination of a quaternary translesion polymerase complex consisting of the Rev1 CTD, the heterodimeric Pol ζ complex, and the Pol κ Rev1-interacting region. Yeast two-hybrid assays were employed to identify important interface residues of the translesion polymerase complex. The structural elucidation of such a quaternary translesion polymerase complex encompassing both insertion and extension polymerases bridged by the Rev1 CTD provides the first molecular explanation of the essential scaffolding function of Rev1 and highlights the Rev1 CTD as a promising target for developing novel cancer therapeutics to suppress translesion synthesis. Our studies support the notion that vertebrate insertion and extension polymerases could structurally cooperate within a megatranslesion polymerase complex (translesionsome) nucleated by Rev1 to achieve efficient lesion bypass without incurring an additional switching mechanism.

Indexed as

Amino Acid SequenceAnimalsCell LineChickensCloning, MolecularCrystallography, X-RayDNA DamageDNA-Directed DNA PolymeraseMagnetic Resonance SpectroscopyMiceModels, MolecularMolecular ConformationMolecular Sequence DataMutagenesis, Site-DirectedNeoplasmsNucleotidyltransferasesDNA-Directed DNA PolymeraseDNA polymerase zetaNucleotidyltransferasesPOLK protein, humanProteinsRev1 protein, mouseY-Family DNA Polymerases

Identifiers

PMID22859295
PMCPMC3460478
OpenAlexW2142881120

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.