Coordination of cell cycle, DNA repair and muscle gene expression in myoblasts exposed to genotoxic stress

Marta Simonatto, Lorenzo Giordani, Fabrizia Marullo, Giulia Claudia Minetti, Pier Lorenzo Puri, Lucia Latella

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Upon exposure to genotoxic stress, skeletal muscle progenitors coordinate DNA repair and the activation of the differentiation program, through the DNA damage-activated differentiation checkpoint, which holds the transcription of differentiation genes while the DNA is repaired. A conceptual hurdle intrinsic to this process relates to the coordination of DNA repair and muscle-specific gene transcription within specific cell cycle boundaries (cell cycle checkpoints) activated by different types of genotoxins. Here we show that in proliferating myoblasts, the inhibition of muscle gene transcription occurs by either a G 1- or G 2-specific differentiation checkpoint. In response to genotoxins that induce G 1 arrest, MyoD binds target genes, but is functionally inactivated by a c-Abl dependent phosphorylation. In contrast, DNA damage-activated G 2 checkpoint relies on the inability of MyoD to bind the chromatin at the G 2 phase of the cell cycle. These results indicate an intimate relationship between DNA damage-activated cell cycle checkpoints and the control of tissue-specific gene expression to allow DNA repair in myoblasts prior to the activation of the differentiation program.

Original languageEnglish
Pages (from-to)2355-2363
Number of pages9
JournalCell Cycle
Volume10
Issue number14
DOIs
Publication statusPublished - Jul 15 2011

Fingerprint

Myoblasts
DNA Repair
DNA Damage
Cell Cycle
Cell Cycle Checkpoints
Gene Expression
Muscles
Mutagens
Genes
Chromatin
Skeletal Muscle
Phosphorylation
DNA

Keywords

  • Cell cycle
  • DNA damage
  • Muscle differentiation
  • MyoD

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Coordination of cell cycle, DNA repair and muscle gene expression in myoblasts exposed to genotoxic stress. / Simonatto, Marta; Giordani, Lorenzo; Marullo, Fabrizia; Minetti, Giulia Claudia; Puri, Pier Lorenzo; Latella, Lucia.

In: Cell Cycle, Vol. 10, No. 14, 15.07.2011, p. 2355-2363.

Research output: Contribution to journalArticle

Simonatto, Marta ; Giordani, Lorenzo ; Marullo, Fabrizia ; Minetti, Giulia Claudia ; Puri, Pier Lorenzo ; Latella, Lucia. / Coordination of cell cycle, DNA repair and muscle gene expression in myoblasts exposed to genotoxic stress. In: Cell Cycle. 2011 ; Vol. 10, No. 14. pp. 2355-2363.
@article{cade40b56b304a17aba76cbc6808420e,
title = "Coordination of cell cycle, DNA repair and muscle gene expression in myoblasts exposed to genotoxic stress",
abstract = "Upon exposure to genotoxic stress, skeletal muscle progenitors coordinate DNA repair and the activation of the differentiation program, through the DNA damage-activated differentiation checkpoint, which holds the transcription of differentiation genes while the DNA is repaired. A conceptual hurdle intrinsic to this process relates to the coordination of DNA repair and muscle-specific gene transcription within specific cell cycle boundaries (cell cycle checkpoints) activated by different types of genotoxins. Here we show that in proliferating myoblasts, the inhibition of muscle gene transcription occurs by either a G 1- or G 2-specific differentiation checkpoint. In response to genotoxins that induce G 1 arrest, MyoD binds target genes, but is functionally inactivated by a c-Abl dependent phosphorylation. In contrast, DNA damage-activated G 2 checkpoint relies on the inability of MyoD to bind the chromatin at the G 2 phase of the cell cycle. These results indicate an intimate relationship between DNA damage-activated cell cycle checkpoints and the control of tissue-specific gene expression to allow DNA repair in myoblasts prior to the activation of the differentiation program.",
keywords = "Cell cycle, DNA damage, Muscle differentiation, MyoD",
author = "Marta Simonatto and Lorenzo Giordani and Fabrizia Marullo and Minetti, {Giulia Claudia} and Puri, {Pier Lorenzo} and Lucia Latella",
year = "2011",
month = "7",
day = "15",
doi = "10.4161/cc.10.14.15948",
language = "English",
volume = "10",
pages = "2355--2363",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "14",

}

TY - JOUR

T1 - Coordination of cell cycle, DNA repair and muscle gene expression in myoblasts exposed to genotoxic stress

AU - Simonatto, Marta

AU - Giordani, Lorenzo

AU - Marullo, Fabrizia

AU - Minetti, Giulia Claudia

AU - Puri, Pier Lorenzo

AU - Latella, Lucia

PY - 2011/7/15

Y1 - 2011/7/15

N2 - Upon exposure to genotoxic stress, skeletal muscle progenitors coordinate DNA repair and the activation of the differentiation program, through the DNA damage-activated differentiation checkpoint, which holds the transcription of differentiation genes while the DNA is repaired. A conceptual hurdle intrinsic to this process relates to the coordination of DNA repair and muscle-specific gene transcription within specific cell cycle boundaries (cell cycle checkpoints) activated by different types of genotoxins. Here we show that in proliferating myoblasts, the inhibition of muscle gene transcription occurs by either a G 1- or G 2-specific differentiation checkpoint. In response to genotoxins that induce G 1 arrest, MyoD binds target genes, but is functionally inactivated by a c-Abl dependent phosphorylation. In contrast, DNA damage-activated G 2 checkpoint relies on the inability of MyoD to bind the chromatin at the G 2 phase of the cell cycle. These results indicate an intimate relationship between DNA damage-activated cell cycle checkpoints and the control of tissue-specific gene expression to allow DNA repair in myoblasts prior to the activation of the differentiation program.

AB - Upon exposure to genotoxic stress, skeletal muscle progenitors coordinate DNA repair and the activation of the differentiation program, through the DNA damage-activated differentiation checkpoint, which holds the transcription of differentiation genes while the DNA is repaired. A conceptual hurdle intrinsic to this process relates to the coordination of DNA repair and muscle-specific gene transcription within specific cell cycle boundaries (cell cycle checkpoints) activated by different types of genotoxins. Here we show that in proliferating myoblasts, the inhibition of muscle gene transcription occurs by either a G 1- or G 2-specific differentiation checkpoint. In response to genotoxins that induce G 1 arrest, MyoD binds target genes, but is functionally inactivated by a c-Abl dependent phosphorylation. In contrast, DNA damage-activated G 2 checkpoint relies on the inability of MyoD to bind the chromatin at the G 2 phase of the cell cycle. These results indicate an intimate relationship between DNA damage-activated cell cycle checkpoints and the control of tissue-specific gene expression to allow DNA repair in myoblasts prior to the activation of the differentiation program.

KW - Cell cycle

KW - DNA damage

KW - Muscle differentiation

KW - MyoD

UR - http://www.scopus.com/inward/record.url?scp=79960437454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960437454&partnerID=8YFLogxK

U2 - 10.4161/cc.10.14.15948

DO - 10.4161/cc.10.14.15948

M3 - Article

C2 - 21685725

AN - SCOPUS:79960437454

VL - 10

SP - 2355

EP - 2363

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 14

ER -