P300-mediated acetylation of TRF2 is required for maintaining functional telomeres

Yoon Ra Her, In Kwon Chung

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The human telomeric protein TRF2 is required to protect chromosome ends by facilitating their organization into the protective capping structure. Post-translational modifications of TRF2 such as phosphorylation, ubiquitination, SUMOylation, methylation and poly(ADP-ribosyl)ation have been shown to play important roles in telomere function. Here we show that TRF2 specifically interacts with the histone acetyltransferase p300, and that p300 acetylates the lysine residue at position 293 of TRF2. We also report that p300-mediated acetylation stabilizes the TRF2 protein by inhibiting its ubiquitin-dependent proteolysis and is required for efficient telomere binding of TRF2. Furthermore, overexpression of the acetylation-deficient mutant, K293R, induces DNA-damage response foci at telomeres, thereby leading to induction of impaired cell growth, cellular senescence and altered cell cycle distribution. A small but significant number of metaphase chromosomes show no telomeric signals at chromatid ends, suggesting an aberrant telomere structure. These findings demonstrate that acetylation of TRF2 by p300 plays a crucial role in the maintenance of functional telomeres as well as in the regulation of the telomere-Associated DNAdamage response, thus providing a new route for modulating telomere protection function.

Original languageEnglish
Pages (from-to)2267-2283
Number of pages17
JournalNucleic acids research
Volume41
Issue number4
DOIs
Publication statusPublished - 2013 Feb 1

Fingerprint

Telomere
Acetylation
Telomeric Repeat Binding Protein 2
Chromosomes
Sumoylation
Histone Acetyltransferases
Chromatids
Cell Aging
Ubiquitination
Post Translational Protein Processing
Metaphase
Ubiquitin
Adenosine Diphosphate
Methylation
Proteolysis
Lysine
DNA Damage
Cell Cycle
Maintenance
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

@article{f0731102e1404528826b1fb746e3ad0a,
title = "P300-mediated acetylation of TRF2 is required for maintaining functional telomeres",
abstract = "The human telomeric protein TRF2 is required to protect chromosome ends by facilitating their organization into the protective capping structure. Post-translational modifications of TRF2 such as phosphorylation, ubiquitination, SUMOylation, methylation and poly(ADP-ribosyl)ation have been shown to play important roles in telomere function. Here we show that TRF2 specifically interacts with the histone acetyltransferase p300, and that p300 acetylates the lysine residue at position 293 of TRF2. We also report that p300-mediated acetylation stabilizes the TRF2 protein by inhibiting its ubiquitin-dependent proteolysis and is required for efficient telomere binding of TRF2. Furthermore, overexpression of the acetylation-deficient mutant, K293R, induces DNA-damage response foci at telomeres, thereby leading to induction of impaired cell growth, cellular senescence and altered cell cycle distribution. A small but significant number of metaphase chromosomes show no telomeric signals at chromatid ends, suggesting an aberrant telomere structure. These findings demonstrate that acetylation of TRF2 by p300 plays a crucial role in the maintenance of functional telomeres as well as in the regulation of the telomere-Associated DNAdamage response, thus providing a new route for modulating telomere protection function.",
author = "Her, {Yoon Ra} and Chung, {In Kwon}",
year = "2013",
month = "2",
day = "1",
doi = "10.1093/nar/gks1354",
language = "English",
volume = "41",
pages = "2267--2283",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "4",

}

P300-mediated acetylation of TRF2 is required for maintaining functional telomeres. / Her, Yoon Ra; Chung, In Kwon.

In: Nucleic acids research, Vol. 41, No. 4, 01.02.2013, p. 2267-2283.

Research output: Contribution to journalArticle

TY - JOUR

T1 - P300-mediated acetylation of TRF2 is required for maintaining functional telomeres

AU - Her, Yoon Ra

AU - Chung, In Kwon

PY - 2013/2/1

Y1 - 2013/2/1

N2 - The human telomeric protein TRF2 is required to protect chromosome ends by facilitating their organization into the protective capping structure. Post-translational modifications of TRF2 such as phosphorylation, ubiquitination, SUMOylation, methylation and poly(ADP-ribosyl)ation have been shown to play important roles in telomere function. Here we show that TRF2 specifically interacts with the histone acetyltransferase p300, and that p300 acetylates the lysine residue at position 293 of TRF2. We also report that p300-mediated acetylation stabilizes the TRF2 protein by inhibiting its ubiquitin-dependent proteolysis and is required for efficient telomere binding of TRF2. Furthermore, overexpression of the acetylation-deficient mutant, K293R, induces DNA-damage response foci at telomeres, thereby leading to induction of impaired cell growth, cellular senescence and altered cell cycle distribution. A small but significant number of metaphase chromosomes show no telomeric signals at chromatid ends, suggesting an aberrant telomere structure. These findings demonstrate that acetylation of TRF2 by p300 plays a crucial role in the maintenance of functional telomeres as well as in the regulation of the telomere-Associated DNAdamage response, thus providing a new route for modulating telomere protection function.

AB - The human telomeric protein TRF2 is required to protect chromosome ends by facilitating their organization into the protective capping structure. Post-translational modifications of TRF2 such as phosphorylation, ubiquitination, SUMOylation, methylation and poly(ADP-ribosyl)ation have been shown to play important roles in telomere function. Here we show that TRF2 specifically interacts with the histone acetyltransferase p300, and that p300 acetylates the lysine residue at position 293 of TRF2. We also report that p300-mediated acetylation stabilizes the TRF2 protein by inhibiting its ubiquitin-dependent proteolysis and is required for efficient telomere binding of TRF2. Furthermore, overexpression of the acetylation-deficient mutant, K293R, induces DNA-damage response foci at telomeres, thereby leading to induction of impaired cell growth, cellular senescence and altered cell cycle distribution. A small but significant number of metaphase chromosomes show no telomeric signals at chromatid ends, suggesting an aberrant telomere structure. These findings demonstrate that acetylation of TRF2 by p300 plays a crucial role in the maintenance of functional telomeres as well as in the regulation of the telomere-Associated DNAdamage response, thus providing a new route for modulating telomere protection function.

UR - http://www.scopus.com/inward/record.url?scp=84876394163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876394163&partnerID=8YFLogxK

U2 - 10.1093/nar/gks1354

DO - 10.1093/nar/gks1354

M3 - Article

VL - 41

SP - 2267

EP - 2283

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 4

ER -