Regulation of DNA polymerase ß by poly(ADP-ribose) polymerase

Sügimura, Takashi; Masutani, Mitsuko; Ogura, Tsutomu; Takenouchi, Nobuko; Ikejima, Miyoko; Esumi, Hiroyasu

doi:10.1007/978-1-4419-8718-1_48

ADP-Ribosylation Reactions 1992

DOI: 10.1007/978-1-4419-8718-1_48

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Regulation of DNA polymerase ß by poly(ADP-ribose) polymerase

Takashi Sügimura¹,

Mitsuko Masutani²,

Tsutomu Ogura³

et al.

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Cited by 2 publications

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Poly(ADP-ribose) catabolism in mammalian cells

Lagueux¹,

Shah²,

M�nard³

et al. 1994

Mol Cell Biochem

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Poly(ADP-ribose) catabolism is a complex situation involving many proteins and DNA. We have developed an in vitro turnover system where poly(ADP-ribose) metabolism is monitored in presence of different relative amounts of two principal enzymes poly(ADP-ribose) transferase and poly(ADP-ribose) glycohydrolase along with other proteins and DNA. Our current results reviewed here show that the quality of polymer, i.e. chain length and complexity, as well as preference for the nuclear substrate varies depending upon the availability of poly(ADP-ribose) glycohydrolase. These results are interpreted in the light of the recent data implicating poly(ADP-ribose) metabolism in DNA-repair.

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Poly(ADP-ribose) catabolism in mammalian cells

Lagueux¹,

Shah²,

M�nard³

et al. 1994

Mol Cell Biochem

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The effects of aging and neurodegeneration on apoptosis-associated DNA fragmentation and the benefits of nicotinamide

Mukherjee

Adams

1997

Molecular and Chemical Neuropathology

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In this work, the tertiary butylhydroperoxide- (t-BuOOH) treated mouse was used as a model to study the oxidative stress that is associated with various neurodegenerative diseases. DNA was found to be an early target of t-BuOOH attack. Necrosis was associated with extensive DNA fragmentation that occurred in almost all regions of the brain within 20 min following intracerebroventricular (icv) injection of 109.7 mg/kg t-BuOOH. Apoptosis was associated with high levels of DNA fragmentation that was observed at 48 h after icv administration of 21.9 mg/kg t-BuOOH. Susceptibility to DNA damage was found to be age-dependent, since 24-mo-old mice exhibited consistently higher and more pervasive DNA damage than 8 mo-old-mice. Extensive DNA damage was seen in various brain regions in patients with Alzheimer disease (AD) and with both Alzheimer and Parkinson disease (AD-PD). These results directly implicate DNA damage in neurodegeneration. The DNA fragmentation ob-served can lead to both apoptosis and necrosis, as suggested by gel electrophoresis. Nicotinamide, a precursor of NAD in the brain, was able to prevent DNA fragmentation induced by low-dose t-BuOOH, when coadministered with the toxin.

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Regulation of DNA polymerase ß by poly(ADP-ribose) polymerase

Cited by 2 publications

References 12 publications

Poly(ADP-ribose) catabolism in mammalian cells

Poly(ADP-ribose) catabolism in mammalian cells

The effects of aging and neurodegeneration on apoptosis-associated DNA fragmentation and the benefits of nicotinamide

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