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Molecular and Cellular Biology, March 2001, p. 1828-1832, Vol. 21, No. 5
Ecole Supérieure de Biotechnologie de
Strasbourg, UPR 9003 du CNRS, Cancérogenèse et
Mutagenèse Moléculaire et
Structurale,1 and Institut de
Génétique et de Biologie Moléculaire et Cellulaire,
CNRS/INSERM/ULP, Collège de France,2 67400 Illkirch Cedex, France, and Genetic Disease Research Branch,
National Human Genome Research Institute, National Institutes of
Health, Bethesda, Maryland 208923
Received 7 November 2000/Accepted 10 November 2000
PARP-1 and ATM are both involved in the response to DNA strand
breaks, resulting in induction of a signaling network responsible for
DNA surveillance, cellular recovery, and cell survival. ATM interacts
with double-strand break repair pathways and induces signals resulting
in the control of the cell cycle-coupled checkpoints. PARP-1 acts as a
DNA break sensor in the base excision repair pathway of DNA. Mice with
mutations inactivating either protein show radiosensitivity and high
radiation-induced chromosomal aberration frequencies. Embryos carrying
double mutations of both PARP-1 and Atm genes
were generated. These mutant embryos show apoptosis in the embryo but
not in extraembryonic tissues and die at embryonic day 8.0, although
extraembryonic tissues appear normal for up to 10.5 days of gestation.
These results reveal a functional synergy between PARP-1 and ATM during
a period of embryogenesis when cell cycle checkpoints are not active
and the embryo is particularly sensitive to DNA damage. These results
suggest that ATM and PARP-1 have synergistic phenotypes due to the
effects of these proteins on signaling DNA damage and/or on distinct
pathways of DNA repair.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.5.1828-1832.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Early Embryonic Lethality in PARP-1 Atm
Double-Mutant Mice Suggests a Functional Synergy in Cell Proliferation
during Development
*
Corresponding author. Mailing address: UPR 9003 du
CNRS, Laboratoire conventionné avec le Commissariat à
l'Energie Atomique, Ecole Supérieure de Biotechnologie de
Strasbourg, Boulevard Sébastien Brant, 67400 Illkirch, France.
Phone: (33) 388 65 53 64. Fax: (33) 388 65 53 52. E-mail:
josiane{at}esbs.u-strasbg.fr.
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