%0 Journal Article
%T Essential role for poly (ADP-ribosyl)ation in mouse preimplantation development
%A Takuya IMAMURA
%A Thi NEILDEZ
%A Catherine THENEVIN
%A Andras PALDI
%J BMC Molecular Biology
%D 2004
%I BioMed Central
%R 10.1186/1471-2199-5-4
%X We have observed strong but transient synthesis of poly ADP-ribose polymers on decondensing chromosomes of fertilized and parthenogenetically activated mouse oocytes. Inhibition of this transient upregulation with a specific enzyme inhibitor, 3-aminobenzamide, has long-term effects on the postimplantation development of the embryos. In addition, inhibition of poly (ADP-ribosyl)ation at the 4¨C8 cell stage selectively blocks morula compaction.These observations suggest that poly (ADP-ribosyl)ation is involved in the epigenetic chromatin remodeling in the zygote.Poly (ADP-ribosyl)ation is a covalent modification of proteins catalyzed by the poly (ADP-ribose) polymerases (PARPs) (for detailed reviews see [1-3]). The modification involves the serial transfer of ADP-ribose moieties from co-enzyme NAD+ to an aspartate, glutamate or lysine residue on the surface of the acceptor protein. The reaction results in an ADP ribose polymer chain of variable length attached to the protein surface. Known natural targets of poly (ADP-ribosyl)ation include many proteins that participate in nuclear and chromatin structure (histones, HMG proteins, lamin B, many transcription factors, DNA replication factors etc). The best characterized mouse enzyme, PARP-1 also controls its own activity by automodification. The negative electric charge of the polymers increases with length of the chain and causes the modified proteins to dissociate resulting in disruption of chromatin structure. The effect is transient, since the poly (ADP-ribosyl) polymers are rapidly degraded by poly (ADP-ribose) glycohydrolase, thus, restoring the initial charge of the protein. It is well established that poly (ADP-ribosyl)ation is implicated in DNA repair, and this function is based on the strong chromatin modifying potential of the modification. The two major poly (ADP-ribose) polymerases, PARP-1 and PARP-2 are strongly activated by single-strand DNA breaks. The chromatin proteins around the site of breakage are rap
%U http://www.biomedcentral.com/1471-2199/5/4