Journal
SCIENCE
Volume 355, Issue 6331, Pages 1312-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aad8242
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Funding
- NCI NIH HHS [R01 CA130996, R01 CA203561] Funding Source: Medline
- NIA NIH HHS [R03 AG052365, P01 AG047200, R37 AG028730, R01 AG027237] Funding Source: Medline
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DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD(+) (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD(+) to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate-ribose) polymerase], a critical DNA repair protein. As mice age and NAD(+) concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD(+). Thus, NAD(+) directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.
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