title: Negative regulation of alkylation-induced sister-chromatid exchange by poly(ADP-ribose) polymerase-1 activity.
abstract: One of the earliest responses to DNA damage in eukaryotic cells is activation of poly(ADP-ribose) polymerase-1 (PARP-1), a DNA strand break-dependent nuclear enzyme which covalently modifies proteins with poly(ADP-ribose). Here, we show that conditional over-expression of PARP-1 in stably transfected hamster cells, which causes cellular over-accumulation of poly(ADP-ribose) by several-fold, strongly suppresses alkylation-induced sister-chromatid exchange (SCE), while cytotoxicity of alkylation treatment is slightly enhanced. Viewed together with the known potentiation of SCE by abrogation of PARP-1 activity, our results provide evidence that PARP-1 activity is an important regulator of alkylation-induced SCE formation, imposing a control that is strictly negative and commensurate with the level of enzyme activity.
authors.affiliation: Deutsches Krebsforschungszentrum, Abteilung Tumorvirologie, Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Meyer
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: S
authors.initials: S
authors.lastname: Beneke
authors.forename: J H
authors.initials: JH
authors.lastname: Küpper
authors.forename: A
authors.initials: A
authors.lastname: Bürkle
mesh_terms: D000478:Alkylation; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D003907:Dexamethasone / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology*; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D012854:Sister Chromatid Exchange
chemical_list: D007527:Isoenzymes; D008769:Methylnitronitrosoguanidine; D003907:Dexamethasone; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases