Poly(etheno ADP-ribose) blocks poly(ADP-ribose) glycohydrolase activity |
| |
Authors: | Shirato Masayasu Tozawa Shunichi Maeda Daisuke Watanabe Masatoshi Nakagama Hitoshi Masutani Mitsuko |
| |
Affiliation: | ADP-ribosylation in Oncology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. mmasutan@gan2.res.ncc.go.jp |
| |
Abstract: | Poly(ADP-ribose) is a biopolymer synthesized by poly(ADP-ribose) polymerases. Recent findings suggest the possibility for modulation of cellular functions including cell death and mitosis by poly(ADP-ribose). Derivatization of poly(ADP-ribose) may be useful for investigating the effects of poly(ADP-ribose) on various cellular processes. We prepared poly(etheno ADP-ribose) (poly(epsilonADP-ribose)) by converting the adenine moiety of poly(ADP-ribose) to 1-N(6)-etheno adenine residues. Poly(epsilonADP-ribose) is shown to be highly resistant to digestion by poly(ADP-ribose) glycohydrolase (Parg). On the other hand, poly(epsilonADP-ribose) could be readily digested by phosphodiesterase. Furthermore, poly(epsilonADP-ribose) inhibited Parg activity to hydrolyse ribose-ribose bonds of poly(ADP-ribose). This study suggests the possibility that poly(epsilonADP-ribose) might be a useful tool for studying the poly(ADP-ribose) dynamics and function of Parg. This study also implies that modification of the adenine moiety of poly(ADP-ribose) abrogates the susceptibility to digestion by Parg. |
| |
Keywords: | Poly(ADP-ribose) glycohydrolase Poly(etheno ADP-ribose) Poly(ADP-ribose) Inhibitor |
本文献已被 ScienceDirect PubMed 等数据库收录! |