Evidence map›Paper›PMID 19332536›Full record

ArticleThe Journal of biological chemistry2009

c-Myc-induced aberrant DNA synthesis and activation of DNA damage response in p300 knockdown cells.

Natesan Sankar, Ravi-Kumar Kadeppagari, Bayar Thimmapaya

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03325517 (Effect of Adenovirus E1A Oncogene on DNA Replication Dynamics), which is not on this map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
0.4field-weighted citation impact, top 36% 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.

NCT03325517 unknown statusnot on this mapstarted 2017, after this paper: background citation

Effect of Adenovirus E1A Oncogene on DNA Replication Dynamics

TypeobservationalSponsorHeba Momen kamelRan2017 to 2019Enrolled50ConditionsAdenovirus
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. The therapeutic potential of RNA m(6)A in lung cancer.Cell communication and signaling : CCS · 2024
    Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. DNA replication stress: oncogenes in the spotlight.Genetics and molecular biology · 2019
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. MYC and the control of DNA replication.Cold Spring Harbor perspectives in medicine · 2014
    Review
  17. Article
  18. Article
  19. Article
  20. Article
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

3 authors at 1 institution in 1 country.

Natesan SankarDepartment of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Ravi-Kumar Kadeppagari
Bayar Thimmapaya
Northwestern University · US

Funding

FUNCTIONS OF AN EIA-ASSOCIATED CELLULAR PROTEINR01CA074403 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI THIMMAPAYA, BAYAR · 1998 to 2010
$2.8M
NCI NIH HHS CA74403
6 · The paper itself

Abstract

We previously showed that in quiescent cells, p300/CBP (CREB-binding protein)family coactivators repress c-myc and prevent premature induction of DNA synthesis. p300/CBP-depleted cells exit G(1) early and continue to accumulate in S phase but do not progress into G(2)/M, and eventually they die of apoptosis. Here, we show that the S-phase arrest in these cells is because of an intra-S-phase block. The inappropriate DNA synthesis that occurs as a result of forced expression of c-myc leads to the activation of the DNA damage response as evidenced by the phosphorylation of several checkpoint related proteins and the formation of foci containing gamma-H2AX. The activation of checkpoint response is related to the induction of c-myc, as the phosphorylation of checkpoint proteins can be reversed when cells are treated with a c-Myc inhibitor or when Myc synthesis is blocked by short hairpin RNA. Using the DNA fiber assay, we show that in p300-depleted cells initiation of replication occurs from multiple replication origins. Chromatin loading of the Cdc45 protein also indicates increased origin activity in p300 knockdown cells. Immunofluorescence experiments indicate that c-Myc colocalizes with replication foci, consistent with the recently reported direct role of c-Myc in the initiation of DNA synthesis. Thus, the inappropriate S-phase entry of p300 down-regulated cells is likely to be because of c-Myc-induced deregulated replication origin activity, which results in replicative stress, activation of a DNA damage response, and S-phase arrest. Our results point to an important role for p300 in maintaining genomic integrity by negatively regulating c-myc.

Indexed as

DNA DamageDNA ReplicationGene Knockdown TechniquesCell Cycle ProteinsCell LineCell ProliferationChromatinDown-RegulationE1A-Associated p300 ProteinHistonesHumansProliferating Cell Nuclear AntigenProtein TransportProto-Oncogene Proteins c-mycReplication OriginRNA, Small InterferingCDC45 protein, humanCell Cycle ProteinsChromatinE1A-Associated p300 ProteinEP300 protein, humanH2AX protein, humanHistonesProliferating Cell Nuclear AntigenProto-Oncogene Proteins c-mycRNA, Small Interfering

Identifiers

PMID19332536
PMCPMC2685700
OpenAlexW2094618322

What OpenQuestion holds

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Registered trials

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.