| Literature DB >> 28336669 |
Jun Li1, Michael S Bonkowski1, Sébastien Moniot2, Dapeng Zhang3, Basil P Hubbard1, Alvin J Y Ling1, Luis A Rajman1, Bo Qin4, Zhenkun Lou4, Vera Gorbunova5, L Aravind3, Clemens Steegborn2, David A Sinclair6,7.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2017 PMID： 28336669 PMCID： PMC5456119 DOI： 10.1126/science.aad8242
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728