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pubmed-article:12533671pubmed:abstractTextAdozelesin is an alkylating minor groove DNA binder that is capable of rapidly inhibiting DNA replication in treated cells through a trans-acting mechanism and preferentially arrests cells in S phase. It has been shown previously that in cells treated with adozelesin, replication protein A (RPA) activity is deficient, and the middle subunit of RPA is hyperphosphorylated. The adozelesin-induced RPA hyperphosphorylation can be blocked by the replicative DNA polymerase inhibitor, aphidicolin, suggesting that adozelesin-triggered cellular DNA damage responses require active DNA replication forks. These data imply that cellular DNA damage responses to adozelesin treatment are preferentially induced in S phase. Here, we show that RPA hyperphosphorylation, RPA intranuclear focalization, and gamma-H2AX intranuclear focalization induced by adozelesin treatment are all dependent on DNA replication fork progression, and focalization is only induced in S phase cells. These findings are similar to those seen with the S phase-specific DNA-damaging agent, camptothecin. Conversely, all three DNA damage responses are independent of either S phase or replication fork progression when induced by treatment with the DNA strand scission agent, C-1027. Furthermore, we demonstrate that adozelesin-induced RPA and gamma-H2AX intranuclear foci appear to colocalize within the nuclei of S phase cells.lld:pubmed
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pubmed-article:12533671pubmed:authorpubmed-author:LiuJen-SingJSlld:pubmed
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pubmed-article:12533671pubmed:authorpubmed-author:MelendyThomas...lld:pubmed
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pubmed-article:12533671pubmed:pagination41-7lld:pubmed
pubmed-article:12533671pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:12533671pubmed:articleTitleInduction of DNA damage responses by adozelesin is S phase-specific and dependent on active replication forks.lld:pubmed
pubmed-article:12533671pubmed:affiliationDepartments of Microbiology and Biochemistry and the Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, SUNY, School of Medicine and Biomedical Sciences, Buffalo, New York 14214, USA.lld:pubmed
pubmed-article:12533671pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:12533671pubmed:publicationTypeComparative Studylld:pubmed
pubmed-article:12533671pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:12533671pubmed:publicationTypeResearch Support, U.S. Gov't, Non-P.H.S.lld:pubmed
pubmed-article:12533671pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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