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The 39‐kDa poly(ADP‐ribose) glycohydrolase, ARH3, hydrolyzes O‐Acetyl‐ADP‐ribose, a product of the Sir2 family of acetyl‐histone deacetylases.
Author(s) -
Ono Tohru,
Kasamatsu Atsushi,
Oka Shunya,
Moss Joel
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a641-e
Subject(s) - ribose , nad+ kinase , biochemistry , poly adp ribose polymerase , acetylation , nicotinamide , chemistry , cyclic adp ribose , histone , hydrolase , enzyme , stereochemistry , biology , dna , polymerase , microbiology and biotechnology , gene , cd38 , stem cell , cd34
The Sir2 family of NAD‐dependent N‐acetyl‐protein deacetylases participates in the regulation of gene silencing, chromatin structure, and longevity. In the Sir2‐catalyzed reaction, the acetyl moiety of N‐acetyl‐histone is transferred to the ADP‐ribose of NAD, yielding O‐acetyl‐ADP‐ribose and nicotinamide. We hypothesized that if O‐acetyl‐ADP‐ribose were an important signaling molecule, a specific hydrolase would cleave the (O‐acetyl)‐(ADP‐ribose) linkage. We report here that the poly(ADP‐ribose) glycohydrolase ARH3, hydrolyzed O‐acetyl‐ADP‐ribose to produce ADP‐ribose in a time‐ and Mg2+‐dependent reaction and thus could participate in two signaling pathways. This O‐acetyl‐ADP‐ribose hydrolase belongs to a family of three, structurally related 39‐kDa ADP‐ribose‐binding proteins (ARH1‐3). ARH1 was reported to hydrolyze ADP‐ribosylarginine, whereas ARH3 degraded poly(ADP‐ribose). ARH3‐catalyzed generation of ADP‐ribose from O‐acetyl‐ADP‐ribose was significantly faster than from poly(ADP‐ribose). Like the degradation of poly(ADP‐ribose) by ARH3, hydrolysis of O‐acetyl‐ADP‐ribose was abolished by replacement of the vicinal aspartates at positions 77 and 78 of ARH3 with alanine. The rate of O‐acetyl‐ADP‐ribose hydrolysis by recombinant ARH3 was 250‐fold that observed with ARH1; ARH2 and poly‐ADP‐ribose glycohydrolase were inactive. All data support the conclusion that the Sir2 reaction product, O‐acetyl‐ADP‐ribose, is degraded by ARH3.