Evidence map›Paper›PMID 29905846›Full record

ArticleNucleic acids research2018

5-Formylcytosine mediated DNA-protein cross-links block DNA replication and induce mutations in human cells.

Shaofei Ji, Iwen Fu, Spandana Naldiga, Hongzhao Shao, Ashis K Basu, Suse Broyde, Natalia Y Tretyakova

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed, 46 citations in OpenAlex.

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  18. Comparative Nucleosomal Reactivity of 5-Formyl-Uridine and 5-Formyl-Cytidine.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Shaofei JiDepartment of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Iwen FuDepartment of Biology, New York University, New York, NY 10003, USA.
Spandana NaldigaDepartment of Chemistry, University of Connecticut, Storrs, CT 06269, USA.
Hongzhao ShaoDepartment of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Ashis K BasuDepartment of Chemistry, University of Connecticut, Storrs, CT 06269, USA.
Suse BroydeDepartment of Biology, New York University, New York, NY 10003, USA.
Natalia Y TretyakovaDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
University of Minnesota · USNew York University · USUniversity of Connecticut · US

Funding

DNA Protein Cross-Links:Cellular Effects and Repair MechanismsR01ES023350 · NIEHS · UNIVERSITY OF MINNESOTA · PI CAMPBELL, COLIN R, TRETYAKOVA, NATALIA Y · 2014 to 2023
$5.0M
DNA Lesion Structures: Mutagenicity and RepairR01CA075449 · NCI · NEW YORK UNIVERSITY · PI BROYDE, SUSE · 1997 to 2015
$4.3M
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
NCI NIH HHS R01 CA075449NIEHS NIH HHS R01 ES023350NIEHS NIH HHS R01 ES025987
6 · The paper itself

Abstract

5-Formylcytosine (5fC) is an epigenetic DNA modification introduced via TET protein-mediated oxidation of 5-methyl-dC. We recently reported that 5fC form reversible DNA-protein conjugates (DPCs) with histone proteins in living cells (Ji et al. (2017) Angew. Chem. Int. Ed., 56:14130-14134). We now examined the effects of 5fC mediated DPCs on DNA replication. Synthetic DNA duplexes containing site-specific DPCs between 5fC and lysine-containing proteins and peptides were subjected to primer extension experiments in the presence of human translesion synthesis DNA polymerases η and κ. We found that DPCs containing histones H2A or H4 completely inhibited DNA replication, but the replication block was removed when the proteins were subjected to proteolytic digestion. Cross-links to 11-mer or 31-mer peptides were bypassed by both polymerases in an error-prone manner, inducing targeted C→T transitions and -1 deletions. Similar types of mutations were observed when plasmids containing 5fC-peptide cross-links were replicated in human embryonic kidney (HEK) 293T cells. Molecular simulations of the 11-mer peptide-dC cross-links bound to human polymerases η and κ revealed that the peptide fits well on the DNA major groove side, and the modified dC forms a stable mismatch with incoming dATP via wobble base pairing in the polymerase active site.

Indexed as

DNA ReplicationMutationCytosineDNADNA-Directed DNA PolymeraseHEK293 CellsHistonesHumansMolecular Dynamics SimulationPeptides5-formylcytosineCytosineDNADNA-Directed DNA PolymeraseHistonesPeptides

Identifiers

PMID29905846
PMCPMC6061883
OpenAlexW2808383642

What OpenQuestion holds

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LicenceCC BY-NC
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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.