Niacin, poly(ADP-ribose) polymerase-1 and genomic stability

Area of Science:

• Biochemistry
• Molecular Biology
• Nutritional Science

Background:

• Niacin (nicotinic acid and nicotinamide) is the precursor to NAD(+), essential for DNA synthesis and PARP-1 enzyme activity.
• Poly(ADP-ribose) polymerase-1 (PARP-1) is crucial for DNA repair, genomic stability, and cellular stress response.
• NAD(+) is the sole substrate for PARP-1, linking niacin status directly to DNA repair mechanisms.

Purpose of the Study:

• To review the absorption, metabolism, and status assessment of niacin.
• To explore the role of PARP-1 in DNA synthesis, repair, and gene expression.
• To discuss the interplay between niacin status, PARP-1 activity, and genomic stability, particularly in relation to tumorigenesis.

Main Methods:

• Review of existing literature on niacin metabolism, PARP-1 function, and genomic stability.
• Analysis of in vitro studies examining NAD(+) depletion and high nicotinamide concentrations on PARP-1 and genomic stability.
• Examination of in vitro and animal studies on niacin deficiency, genotoxic stress, and tumorigenesis.

Main Results:

• Impaired PARP-1 function and reduced genomic stability observed in cells with NAD(+) depletion or high NAM concentrations.
• Niacin deficiency exacerbates genomic instability, especially under genotoxic and oxidative stress, potentially increasing cancer risk.
• Preliminary evidence suggests niacin may offer protection against UV-induced skin tumors in mice; human data is lacking.

Conclusions:

• Niacin status is critical for maintaining genomic stability through PARP-1 activity.
• Both niacin deficiency and potential NAM-induced PARP-1 inhibition can compromise genomic integrity.
• Further research is needed to establish optimal niacin intake levels for genomic stability and cancer prevention in humans.