title: A systematic analysis of the PARP protein family identifies new functions critical for cell physiology.
abstract: The poly(ADP-ribose) polymerase (PARP) family of proteins use NAD(+) as their substrate to modify acceptor proteins with ADP-ribose modifications. The function of most PARPs under physiological conditions is unknown. Here, to better understand this protein family, we systematically analyse the cell cycle localization of each PARP and of poly(ADP-ribose), a product of PARP activity, then identify the knockdown phenotype of each protein and perform secondary assays to elucidate function. We show that most PARPs are cytoplasmic, identify cell cycle differences in the ratio of nuclear to cytoplasmic poly(ADP-ribose) and identify four phenotypic classes of PARP function. These include the regulation of membrane structures, cell viability, cell division and the actin cytoskeleton. Further analysis of PARP14 shows that it is a component of focal adhesion complexes required for proper cell motility and focal adhesion function. In total, we show that PARP proteins are critical regulators of eukaryotic physiology.
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Sejal
authors.initials: S
authors.lastname: Vyas
authors.forename: Melissa
authors.initials: M
authors.lastname: Chesarone-Cataldo
authors.forename: Tanya
authors.initials: T
authors.lastname: Todorova
authors.forename: Yun-Han
authors.initials: YH
authors.lastname: Huang
authors.forename: Paul
authors.initials: P
authors.lastname: Chang
mesh_terms: D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D002467:Cell Nucleus / Q000201:enzymology; D002468:Cell Physiological Phenomena; D048430:Cell Shape; D022001:Focal Adhesions / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D010641:Phenotype; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases
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