PARP-1, PARP-2 and ATM in the DNA damage response: functional synergy in mouse development

Poly(ADP-ribosyl)ation is an immediate DNA damage-dependent posttranslational modification of histones and nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP-ribose) polymerases (PARPs) now constitute a superfamily of 18 proteins, encoded by different genes an...

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Bibliographic Details
Published in:DNA Repair 2004-08, Vol.3 (8), p.1103-1108
Main Authors: Huber, Aline, Bai, Peter, Murcia, Josiane Ménissier de, Murcia, Gilbert de
Format: Article
Language:English
Subjects:
Animals
Ataxia Telangiectasia Mutated Proteins
ATM
Catalytic Domain
Cell Cycle Proteins
Cell Proliferation
DNA Damage
DNA Repair
DNA-Binding Proteins
Gene Expression Regulation, Developmental
Heterozygote
Histones - metabolism
Humans
Mice
Models, Biological
Oxidative Stress
PARP-1
PARP-2
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases - metabolism
Poly(ADP-ribose) Polymerases - physiology
Protein-Serine-Threonine Kinases - metabolism
Protein-Serine-Threonine Kinases - physiology
Signal Transduction
Tumor Suppressor Proteins
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Summary:Poly(ADP-ribosyl)ation is an immediate DNA damage-dependent posttranslational modification of histones and nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP-ribose) polymerases (PARPs) now constitute a superfamily of 18 proteins, encoded by different genes and displaying a common conserved catalytic domain. PARP-1 (113 kDa), the founding member, and PARP-2 (62 kDa) are both involved in DNA-break sensing and signaling when single strand break repair (SSBR) or base excision repair (BER) pathways are engaged. The generation by homologous recombination of deficient mouse models have confirmed the caretaker function of PARP-1 and PARP-2 in mammalian cells under genotoxic stress. This review summarizes our present knowledge on their physiological role in the cellular response to DNA damage and on the genetic interactions between PARP-1, PARP-2, Atm that play an essential role during early embryogenesis.
ISSN:1568-7864
1568-7856
DOI:10.1016/j.dnarep.2004.06.002