Evidence map›Paper›PMID 22148158›Full record

ArticleBiochemistry2012

Searching for DNA lesions: structural evidence for lower- and higher-affinity DNA binding conformations of human alkyladenine DNA glycosylase.

Jeremy W Setser, Gondichatnahalli M Lingaraju, C Ainsley Davis, Leona D Samson, Catherine L Drennan

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

16 citing papers in PubMed, 25 citations in OpenAlex.

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  7. Target search and recognition mechanisms of glycosylase AlkD revealed by scanning FRET-FCS and Markov state models.Proceedings of the National Academy of Sciences of the United States of America · 2020
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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

5 authors at 3 institutions in 1 country.

Jeremy W SetserChemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Gondichatnahalli M Lingaraju
C Ainsley Davis
Leona D Samson
Catherine L Drennan
Center for Environmental Health · USHoward Hughes Medical Institute · USMassachusetts Institute of Technology · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6M
EUKARYTIC DNA ALKYLATION REPAIRR01CA055042 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SAMSON, LEONA D. · 1991 to 2010
$4.8M
X-ray studies of metalloenzyme regulation and catalysisR01GM065337 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI DRENNAN, CATHERINE L · 2002 to 2008
$1.8M
Howard Hughes Medical InstituteNCI NIH HHS CA055042NCI NIH HHS CA092584NCI NIH HHS P01 CA092584NIEHS NIH HHS P30 ES002109NIEHS NIH HHS P30-ES002109NIGMS NIH HHS GM65337NIGMS NIH HHS GM65337-03S2
6 · The paper itself

Abstract

To efficiently repair DNA, human alkyladenine DNA glycosylase (AAG) must search the million-fold excess of unmodified DNA bases to find a handful of DNA lesions. Such a search can be facilitated by the ability of glycosylases, like AAG, to interact with DNA using two affinities: a lower-affinity interaction in a searching process and a higher-affinity interaction for catalytic repair. Here, we present crystal structures of AAG trapped in two DNA-bound states. The lower-affinity depiction allows us to investigate, for the first time, the conformation of this protein in the absence of a tightly bound DNA adduct. We find that active site residues of AAG involved in binding lesion bases are in a disordered state. Furthermore, two loops that contribute significantly to the positive electrostatic surface of AAG are disordered. Additionally, a higher-affinity state of AAG captured here provides a fortuitous snapshot of how this enzyme interacts with a DNA adduct that resembles a one-base loop.

Indexed as

DNA DamageCatalysisCrystallography, X-RayDNA AdductsDNA-Binding ProteinsDNA GlycosylasesDNA RepairGenome, HumanHumansMutagenesisNucleic Acid HeteroduplexesPlasmidsProtein Conformation3-methyladenine-DNA glycosylaseDNA AdductsDNA-Binding ProteinsDNA GlycosylasesNucleic Acid Heteroduplexes

Identifiers

PMID22148158
PMCPMC3254189
OpenAlexW1980349853

What OpenQuestion holds

Textmetadata
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.