| Title | : | A conserved NAD+ binding pocket that regulates protein-protein interactions during aging |
| Authors | : | Jun Li, Michael S Bonkowski, Sébastien Moniot, Dapeng Zhang, Basil P Hubbard, Alvin J Y Ling, Luis A Rajman, Bo Qin, Zhenkun Lou, Vera Gorbunova, L Aravind, Clemens Steegborn, David A Sinclair |
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.
PDF: A conserved NAD+ binding pocket that regulates protein-protein interactions during aging
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