ADP-ribosyl acceptor hydrolase 3 (ARH3) polypeptides and methods of use
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsJoel Moss, Shunya Oka, Jiro Kato, Jianfeng Zhu, Atsushi Kasamatsu
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Abstract
This disclosure provides methods for catalyzing the release of ADP-ribose from poly(ADP-ribose) or O-acetyl-ADP-ribose. Also provided are methods for modifying DNA repair or chromatin structure by introducing into the cell an agent that modifies the activity of an ARH3 polypeptide, or variant or fragment thereof. Further provided are methods for screening molecules involved in the poly(ADP-ribosyl)ation of proteins or O-acetyl-ADP-ribose content, and method for treating disorders by altering activity of an ARH3 protein.
Claims19
A method for catalyzing the release of ADP-ribose from poly(ADP-ribose) or O-acetyl-ADP-ribose, comprising
- contacting the poly(ADP-ribose) or O-acetyl-ADP-ribose with an isolated ADP-ribosyl acceptor hydrolase 3 (ARH3) polypeptide, wherein the ARH3 polypeptide comprises:
- a) the amino acid sequence set forth as one of SEQ ID NO:
- 2, 3, 4, or 6;
- b) an amino acid sequence at least 95% identical to the amino acid sequence set forth as SEQ ID NO:
- 2, wherein the polypeptide has poly(ADP-ribose) glycohydrolase activity or O-acetyl-ADP-ribose hydrolase activity;
- c) the amino acid sequence set forth as SEQ ID NO:
- 2, wherein a glutamic acid is substituted for a glutamine at positions 261 and 262;
- or
- d) the amino acid sequence set forth as SEQ ID NO:
- 2, wherein a glutamic acid is substituted for a glutamine at positions 238 and 239;
- thereby catalyzing the release of ADP ribose.
Dependencies are inferred from the claim text.