Structural highlights
Function
[PARG_RAT] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. PARG acts both as an endo- and exoglycosidase, releasing PAR of different length as well as ADP-ribose monomers. Required for retinoid acid-dependent gene transactivation, probably by dePARsylating histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters (By similarity).
Publication Abstract from PubMed
Reversible post-translational modification by poly(ADP-ribose) (PAR) regulates chromatin structure, DNA repair and cell fate in response to genotoxic stress. PAR glycohydrolase (PARG) removes PAR chains from poly ADP-ribosylated proteins to restore protein function and release oligo(ADP-ribose) chains to signal damage. Here we report crystal structures of mammalian PARG and its complex with a substrate mimic that reveal an open substrate-binding site and a unique 'tyrosine clasp' enabling endoglycosidic cleavage of branched PAR chains.
Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a substrate-binding element.,Kim IK, Kiefer JR, Ho CM, Stegeman RA, Classen S, Tainer JA, Ellenberger T Nat Struct Mol Biol. 2012 May 20;19(6):653-6. doi: 10.1038/nsmb.2305. PMID:22609859[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kim IK, Kiefer JR, Ho CM, Stegeman RA, Classen S, Tainer JA, Ellenberger T. Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a substrate-binding element. Nat Struct Mol Biol. 2012 May 20;19(6):653-6. doi: 10.1038/nsmb.2305. PMID:22609859 doi:10.1038/nsmb.2305
