Evidence map›Paper›PMID 35790757›Full record

ArticleNature communications2022

Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair.

Qun Tang, Mitchell Gulkis, Robert McKenna, Melike Çağlayan

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

10 citing papers in PubMed, 26 citations in OpenAlex.

  1. A sibling study of variation in parental mutation rates.bioRxiv : the preprint server for biology · 2026
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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

4 authors at 1 institution in 1 country.

Qun TangDepartment of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, 32610, USA.
Mitchell GulkisDepartment of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, 32610, USA.ORCID 0000-0001-5831-8802
Robert McKennaDepartment of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, 32610, USA.
Melike ÇağlayanDepartment of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, 32610, USA. caglayanm@ufl.edu.ORCID 0000-0003-1107-1042
University of Florida · US

Funding

Training and OutreachP30GM124166 · NIGMS · CORNELL UNIVERSITY · PI RICHARD A. CERIONE · 2019 to 2026
$28.3M
DNA ligase activities during base excision repair coordinationR35GM147111 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI MELIKE CAGLAYAN · 2022 to 2026
$2.1M
Oxidant and environmental toxicant-induced effects compromise ligation in DNA repairR00ES026191 · NIEHS · UNIVERSITY OF FLORIDA · PI CAGLAYAN, MELIKE · 2018 to 2020
$730k
NIEHS NIH HHS R00 ES026191NIGMS NIH HHS P30 GM124166NIGMS NIH HHS R35 GM147111
6 · The paper itself

Abstract

DNA ligase I (LIG1) catalyzes the ligation of the nick repair intermediate after gap filling by DNA polymerase (pol) β during downstream steps of the base excision repair (BER) pathway. However, how LIG1 discriminates against the mutagenic 3'-mismatches incorporated by polβ at atomic resolution remains undefined. Here, we determine the X-ray structures of LIG1/nick DNA complexes with G:T and A:C mismatches and uncover the ligase strategies that favor or deter the ligation of base substitution errors. Our structures reveal that the LIG1 active site can accommodate a G:T mismatch in the wobble conformation, where an adenylate (AMP) is transferred to the 5'-phosphate of a nick (DNA-AMP), while it stays in the LIG1-AMP intermediate during the initial step of the ligation reaction in the presence of an A:C mismatch at the 3'-strand. Moreover, we show mutagenic ligation and aberrant nick sealing of dG:T and dA:C mismatches, respectively. Finally, we demonstrate that AP-endonuclease 1 (APE1), as a compensatory proofreading enzyme, removes the mismatched bases and interacts with LIG1 at the final BER steps. Our overall findings provide the features of accurate versus mutagenic outcomes coordinated by a multiprotein complex including polβ, LIG1, and APE1 to maintain efficient repair.

Indexed as

DNA RepairMutagensAdenosine MonophosphateDNAMutagenesisAdenosine MonophosphateDNAMutagens

Identifiers

PMID35790757
PMCPMC9256674
OpenAlexW4283815994

What OpenQuestion holds

Textmetadata
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.