Evidence map›Paper›PMID 17616978›Full record

ArticlePLoS genetics2007

RETRACTED: DNA damage, homology-directed repair, and DNA methylation.

Concetta Cuozzo, Antonio Porcellini, Tiziana Angrisano, Annalisa Morano, Bongyong Lee, Alba Di Pardo, Samantha Messina, Rodolfo Iuliano, Alfredo Fusco, Maria R Santillo and 4 more

RetractedErratum issuedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in PLoS genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 108 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed, 2 pooled it
2.9field-weighted citation impact, top 9% 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

108 citing papers in PubMed, 2 syntheses or guidelines pooled it, 192 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Article
  6. Epigenetic networks coordinate DNA methylation across the genome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Somatic mutation as an explanation for epigenetic aging.bioRxiv : the preprint server for biology · 2023
    Article
  13. Article
  14. Article
  15. Inflammation and DNA damage: cause, effect or both.Nature reviews. Rheumatology · 2023
    Review
  16. Article
  17. DNA Methylation of the Dopamine TransporterInternational journal of molecular sciences · 2023
    Article
  18. Review
  19. Article
  20. Methylation in the Promoter Region of the Dopamine TransporterInternational journal of environmental research and public health · 2022
    Article

48 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 2 countries.

Concetta CuozzoDipartimento di Biologia e Patologia Molecolare e Cellulare, Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Università Federico II, Naples, Italy.
Antonio Porcellini
Tiziana Angrisano
Annalisa Morano
Bongyong Lee
Alba Di Pardo
Samantha Messina
Rodolfo Iuliano
Alfredo Fusco
Maria R Santillo
Mark T Muller
Lorenzo Chiariotti
Max E Gottesman
Enrico V Avvedimento
Institute for Experimental Endocrinology and Oncology · ITIstituto Neurologico Mediterraneo · ITUniversity of Central Florida · USColumbia University Irving Medical Center · USSapienza University of Rome · ITUniversity of Naples Federico II · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To explore the link between DNA damage and gene silencing, we induced a DNA double-strand break in the genome of Hela or mouse embryonic stem (ES) cells using I-SceI restriction endonuclease. The I-SceI site lies within one copy of two inactivated tandem repeated green fluorescent protein (GFP) genes (DR-GFP). A total of 2%-4% of the cells generated a functional GFP by homology-directed repair (HR) and gene conversion. However, approximately 50% of these recombinants expressed GFP poorly. Silencing was rapid and associated with HR and DNA methylation of the recombinant gene, since it was prevented in Hela cells by 5-aza-2'-deoxycytidine. ES cells deficient in DNA methyl transferase 1 yielded as many recombinants as wild-type cells, but most of these recombinants expressed GFP robustly. Half of the HR DNA molecules were de novo methylated, principally downstream to the double-strand break, and half were undermethylated relative to the uncut DNA. Methylation of the repaired gene was independent of the methylation status of the converting template. The methylation pattern of recombinant molecules derived from pools of cells carrying DR-GFP at different loci, or from an individual clone carrying DR-GFP at a single locus, was comparable. ClustalW analysis of the sequenced GFP molecules in Hela and ES cells distinguished recombinant and nonrecombinant DNA solely on the basis of their methylation profile and indicated that HR superimposed novel methylation profiles on top of the old patterns. Chromatin immunoprecipitation and RNA analysis revealed that DNA methyl transferase 1 was bound specifically to HR GFP DNA and that methylation of the repaired segment contributed to the silencing of GFP expression. Taken together, our data support a mechanistic link between HR and DNA methylation and suggest that DNA methylation in eukaryotes marks homologous recombined segments.

Indexed as

DNA DamageDNA MethylationDNA RepairAnimalsBase SequenceCell LineChromatinCpG IslandsDNA Breaks, Double-StrandedDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA PrimersGene ExpressionGene SilencingGreen Fluorescent ProteinsHeLa CellsChromatinDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA PrimersGreen Fluorescent ProteinsRecombinant ProteinsRNA, Messenger

Identifiers

PMID17616978
PMCPMC1913100
OpenAlexW2050646440

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.