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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2014

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Nuclear receptor-induced transcription is driven by spatially and timely restricted waves of ROS: The role of Akt, IKK[alpha], and DNA damage repair enzymes

Anno di pubblicazione: 2014

Formato: Cartaceo

Autori: Perillo B.; Santi A.D.; Cernera G.; Ombra M.N.; Castoria G.; Migliaccio A.

Affiliazioni autori: Istituto di Scienze dell'Alimentazione, Avellino, Italy; Dipartimento di Biochimica Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, Naples, Italy

Autori CNR:

  • MARIA NEVE OMBRA

Lingua: inglese

Abstract: Gene expression is governed by chromatin mainly through posttranslational modifications at the N-terminal tails of nucleosomal histone proteins. According to the histone code theory, peculiar sets of such modifications (marks) give rise to reproducible final effects on transcription and, very recently, a further level of complexity has been highlighted in binary switches between specific marks at adjacent residues. In particular, disappearance of dimethyl-lysine 9 in histone H3 is faced by phosphorylation of the following serine during activation of gene expression. Demethylation of lysine 9 by the lysine-specific demethylase 1 (LSD1) is a pre-requisite for addition of the phosphoryl mark to serine 10 and an essential step in the transcriptional control by estrogens. It generates a local burst of oxygen reactive species (ROS) that induce oxidation of nearby nucleotides and recruitment of repair enzymes with a consequent formation of single or double stranded nicks on DNA that modify chromatin flexibility in order to allow correct assembly of the transcriptional machinery. We describe here the molecular mechanism by which members of the family of nuclear receptors prevent the potential damage to DNA during transcription of target genes elicited by the use of ROS to shape chromatin. The mechanism is based on the presence of phosphorylated serine 10 in histone H3 to prevent unbalanced DNA oxidation waves. We also discuss the opportunities raised by the use of voluntary derangement of this servo system to induce selective death in hormone-responsive transformed cells.

Lingua abstract: inglese

Pagine da: 482

Pagine a: 491

Pagine totali: 10

Rivista:

Nucleus Landes Bioscience
Paese di pubblicazione: Stati Uniti d'America
Lingua: inglese
ISSN: 1949-1034

Numero volume: 5

Numero fascicolo: 5

DOI: 10.4161/nucl.36274

Referee: Sì: Internazionale

Indicizzato da:

  • Scopus [2-s2.0-84908181176]
  • ISI Web of Science (WOS) [000342194200015]

Parole chiave:

  • Akt
  • Apoptosis
  • DNA oxidation
  • DNA repair
  • Epigenetic marks
  • Estrogen
  • IKK[alpha]
  • Nuclear receptors
  • Retinoic acid
  • Transcription

URL: http://www.tandfonline.com/doi/full/10.4161/nucl.36274#abstract

Strutture CNR:

 
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