title: ATM and ATR activities maintain replication fork integrity during SV40 chromatin replication.
abstract: Mutation of DNA damage checkpoint signaling kinases ataxia telangiectasia-mutated (ATM) or ATM- and Rad3-related (ATR) results in genomic instability disorders. However, it is not well understood how the instability observed in these syndromes relates to DNA replication/repair defects and failed checkpoint control of cell cycling. As a simple model to address this question, we have studied SV40 chromatin replication in infected cells in the presence of inhibitors of ATM and ATR activities. Two-dimensional gel electrophoresis and southern blotting of SV40 chromatin replication products reveal that ATM activity prevents accumulation of unidirectional replication products, implying that ATM promotes repair of replication-associated double strand breaks. ATR activity alleviates breakage of a functional fork as it converges with a stalled fork. The results suggest that during SV40 chromatin replication, endogenous replication stress activates ATM and ATR signaling, orchestrating the assembly of genome maintenance machinery on viral replication intermediates.
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Vanderbilt Ingram Comprehensive Cancer Center, Nashville, Tennessee, United States of America.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Sowd
authors.forename: Nancy Yan
authors.initials: NY
authors.lastname: Li
authors.forename: Ellen
authors.initials: E
authors.lastname: Fanning
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011753:Pyrones / Q000494:pharmacology; D013539:Simian virus 40 / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
chemical_list: C495818:2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one; D002843:Chromatin; D009025:Morpholines; D010726:Phosphodiesterase Inhibitors; D011753:Pyrones; D002110:Caffeine; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins