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DNA repair defect in poly(ADP-ribose) polymerase-deficient cell lines
C Trucco1, F J Oliver, G de Murcia
1UPR 9003 du Centre National de la Recherche Scientifique, Laboratoire Conventionné avec le Commissariat à l'Energie Atomique, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, F-67400 Illkirch-Graffenstad, France.
Nucleic Acids Research
|May 21, 1998
Summary
Poly(ADP-ribose) polymerase (PARP) is crucial for DNA repair. PARP-deficient mice exhibit extreme sensitivity to DNA-damaging agents, highlighting PARP's role in cellular survival.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Poly(ADP-ribose) polymerase (PARP) plays a role in DNA repair.
- PARP-deficient mice (-/-) show increased sensitivity to DNA damaging agents like N-methyl-N-nitrosourea (MNU) and gamma-irradiation.
Purpose of the Study:
- To investigate the physiological function of PARP.
- To analyze the cause of increased lethality in PARP -/- mice.
Main Methods:
- Gene targeting to generate PARP -/- mice.
- Analysis of primary and immortalized mouse embryonic fibroblasts (MEFs) from PARP -/- mice.
- Treatment with methylmethanesulfonate (MMS) and assessment of cell viability, DNA repair, and cell cycle progression.
Main Results:
- PARP deficiency leads to increased sensitivity to methylmethanesulfonate (MMS).
- Lack of PARP causes cell growth retardation, G2/M cell cycle arrest, and chromosome instability.
- A significant delay in DNA strand-break resealing was observed in PARP -/- cells after MMS treatment.
- Transient expression of the PARP gene restored cell viability following MMS treatment.
Conclusions:
- PARP is essential for efficient base excision repair in vivo.
- PARP acts as a critical survival factor in cells experiencing genotoxic stress.