title: PARP is involved in replicative aging in Neurospora crassa.
abstract: Modification of proteins by the addition of poly(ADP-ribose) is carried out by poly(ADP-ribose) polymerases (PARPs). PARPs have been implicated in a wide range of biological processes in eukaryotes, but no universal function has been established. A study of the Aspergillus nidulans PARP ortholog (PrpA) revealed that the protein is essential and involved in DNA repair, reminiscent of findings using mammalian systems. We found that a Neurospora PARP orthologue (NPO) is dispensable for cell survival, DNA repair and epigenetic silencing but that replicative aging of mycelia is accelerated in an npo mutant strain. We propose that PARPs may control aging as proposed for Sirtuins, which also consume NAD+ and function either as mono(ADP-ribose) transferases or protein deacetylases. PARPs may regulate aging by impacting NAD+/NAM availability, thereby influencing Sirtuin activity, or they may function in alternative NAD+-dependent or NAD+-independent aging pathways.
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, United States. gok1@psu.edu <gok1@psu.edu>
authors.forename: Gregory O
authors.initials: GO
authors.lastname: Kothe
authors.forename: Maki
authors.initials: M
authors.lastname: Kitamura
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Masutani
authors.forename: Eric U
authors.initials: EU
authors.lastname: Selker
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004261:DNA Replication; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D009492:Neurospora crassa / Q000201:enzymology* / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D037761:Sirtuins / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases; D037761:Sirtuins