Poly(ADP-ribosyl)ation is a post-translational modification of proteins that is mediated by poly(ADP-ribose) polymerases (PARPs).Although the existence and nature of the nucleic acid-like molecule poly(ADP-ribose) (PAR) has been known for 40 years, understanding its biological functions-originally thought to be only the regulation of chromatin superstructure when DNA is broken-is still the subject of intense research. Here, we review the mechanisms controlling the biosynthesis of this complex macromolecule and some of its main biological functions, with an emphasis on the most recent advances and hypotheses that have developed in this rapidly growing field.

OrgaNizatiON 125 2 addendum addendum characterization and molecular modeling using the previously reported crystal structures of parp1, parp2, parp3 and parp12 catalytic domains, the authors could subdivide the parp family into three subfamilies. One with authentic parp activity (parp1, parp2, parp3, vparp, tankyrase 1 and tankyrase 2), a second with Mart activity (parp6, tiparp, parp-8, parp10, parp11, parp12, parp14, parp15 and parp16) and a third without catalytic activity (parp9 and parp13). in the review "the expanding field of poly(aDp-ribosyl)ation reactions" by Hakmé et al, one of our "in need of answer" questions was: are some poly(aDp-ribose) polymerase (parp) family members really mono(aDp-ribose) transferases? if so, what determines their different enzymatic activity? the answer to these questions was reported in a recent issue of Molecular Cell (2008, 32: 57-69) in which Kleine and co-workers showed that some of the parp family members have transferase instead of polymerase activity. they proposed the molecular basis for substrate-assisted catalysis, which limits the activity of parp10 to mono(aDpribosyl)ation. On the basis of sequence alignments, biochemical

The macroPARPs Parp-9 and Parp-14 are macro domain containing poly(ADP-ribose) polymerases involved in transcriptional regulation in response to immunoregulatory cytokines. Their genes reside in the same locus (16B3), and the Parp-9 gene lies head-to-head and shares its promoter with the gene encoding its partner, Bbap. Here, we provide a detailed analysis of Parp-9, Parp-14, and Bbap expression during mouse development and adulthood. Parp-9 is developmentally regulated, and prominently expressed in the thymus and specific regions of the brain and gut. In adults, highest expression is maintained in the thymus and intestine. Parp-14 is more weakly expressed, mainly in the thymus during development and in adulthood. In addition, we show that Bbap is essentially coexpressed with Parp-9 during development and in adult mouse. However, the different levels of their transcripts detected in the developing brain and gut suggest that Bbap and Parp-9 display both common and independent tissue-specific regulations.