Evidence map›Paper›PMID 20373772›Full record

ArticleBiochemistry2010

Cross-link structure affects replication-independent DNA interstrand cross-link repair in mammalian cells.

Erica M Hlavin, Michael B Smeaton, Anne M Noronha, Christopher J Wilds, Paul S Miller

Abstract read
In one paragraph

Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

30 citing papers in PubMed, 44 citations in OpenAlex.

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  10. The Fanconi Anemia Pathway in Cancer.Annual review of cancer biology · 2019
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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 2 institutions in 2 countries.

Erica M HlavinDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205, USA.
Michael B Smeaton
Anne M Noronha
Christopher J Wilds
Paul S Miller
Johns Hopkins University · USConcordia University · CA

Funding

TRAINING IN AREAS FUNDAMENTAL TO CANCER RESEARCHT32CA009110 · NCI · JOHNS HOPKINS UNIVERSITY · PI MATUNIS, MICHAEL J., WEERARATNA, ASHANI T · 1985 to 2025
$13.1M
PHARMACOLOGY OF CYCLOPHOSPHAMIDE AND OTHER ALYKLATORSR01CA016783 · NCI · JOHNS HOPKINS UNIVERSITY · PI LUDEMAN, SUSAN M · 1985 to 2009
$2.8M
REPAIR OF INTERSTRAND CROSS LINKED SYNTHETIC DNAR01CA082785 · NCI · JOHNS HOPKINS UNIVERSITY · PI MILLER, PAUL S. · 2000 to 2007
$2.7M
Repair of Interstrand Cross-linked Synthetic DNAR56CA082785 · NCI · JOHNS HOPKINS UNIVERSITY · PI MILLER, PAUL S. · 2009 to 2009
$382k
NCI NIH HHS CA016783NCI NIH HHS CA082785NCI NIH HHS R01 CA016783NCI NIH HHS R01 CA082785NCI NIH HHS R56 CA082785NCI NIH HHS T32 CA009110NCI NIH HHS T32CA09110
6 · The paper itself

Abstract

DNA interstrand cross-links (ICLs) are cytotoxic products of common anticancer drugs and cellular metabolic processes, whose mechanism(s) of repair remains poorly understood. In this study, we show that cross-link structure affects ICL repair in nonreplicating reporter plasmids that contain a mispaired N(4)C-ethyl-N(4)C (C-C), N3T-ethyl-N3T (T-T), or N1I-ethyl-N3T (I-T) ICL. The T-T and I-T cross-links obstruct the hydrogen bond face of the base and mimic the N1G-ethyl-N3C ICL created by bis-chloroethylnitrosourea, whereas the C-C cross-link does not interfere with base pair formation. Host-cell reactivation (HCR) assays in human and hamster cells showed that repair of these ICLs primarily involves the transcription-coupled nucleotide excision repair (TC-NER) pathway. Repair of the C-C ICL was 5-fold more efficient than repair of the T-T or I-T ICLs, suggesting the latter cross-links hinder lesion bypass following initial ICL unhooking. The level of luciferase expression from plasmids containing a C-C cross-link remnant on either the transcribed or nontranscribed strand increased in NER-deficient cells, indicating NER involvement occurs at a step prior to remnant removal, whereas expression from similar T-T remnant plasmids was inhibited in NER-deficient cells, demonstrating NER is required for remnant removal. Sequence analysis of repaired plasmids showed a high proportion of C residues inserted at the site of the T-T and I-T cross-links, and HCR assays showed that Rev1 was likely responsible for these insertions. In contrast, both C and G residues were inserted at the C-C cross-link site, and Rev1 was not required for repair, suggesting replicative or other translesion polymerases can bypass the C-C remnant.

Indexed as

DNA RepairDNA ReplicationAnimalsAntineoplastic Combined Chemotherapy ProtocolsCricetinaeCyclophosphamideDNADNA Breaks, Double-StrandedDNA DamageDoxorubicinHeLa CellsHumansNucleic Acid ConformationRecombination, GeneticVincristineCyclophosphamideDNADoxorubicinVincristine

Identifiers

PMID20373772
PMCPMC2864352
OpenAlexW2001243979

What OpenQuestion holds

Textmetadata
LicenceTDM
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.