title: Acetylation regulates the DNA end-trimming activity of DNA polymerase beta.
abstract: We describe a novel regulatory mechanism for DNA polymerase beta (Polbeta), a protein involved in DNA base excision repair (BER). Polbeta colocalized in vivo and formed a complex with the transcriptional coactivator p300. p300 interacted with Polbeta through distinct domains and acetylated Polbeta in vitro. Polbeta acetylation was furthermore observed in vivo. Lysine 72 of Polbeta was identified as the main target for acetylation by p300. Interestingly, acetylated Polbeta showed a severely reduced ability to participate in a reconstituted BER assay. This was due to an impairment of the dRP-lyase activity of Polbeta. Acetylation of Polbeta thus acts as an intranuclear regulatory mechanism and implies that p300 plays a critical regulatory role in BER.
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Sameez
authors.initials: S
authors.lastname: Hasan
authors.forename: Nazim
authors.initials: N
authors.lastname: El-Andaloussi
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hardeland
authors.forename: Paul O
authors.initials: PO
authors.lastname: Hassa
authors.forename: Christine
authors.initials: C
authors.lastname: Bürki
authors.forename: Ralph
authors.initials: R
authors.lastname: Imhof
authors.forename: Primo
authors.initials: P
authors.lastname: Schär
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
mesh_terms: D000107:Acetylation; D020137:Base Pair Mismatch; D002460:Cell Line; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019951:DNA Polymerase beta / Q000378:metabolism*; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000737:chemistry; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D004247:DNA; D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase; D008239:Lysine