Linked Life Data

12533671

Source:http://linkedlifedata.com/resource/pubmed/id/12533671

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-1-20
pubmed:abstractText
Adozelesin 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Aminoglycosides, http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Alkylating, http://linkedlifedata.com/resource/pubmed/chemical/Aphidicolin, http://linkedlifedata.com/resource/pubmed/chemical/C 1027, http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin, http://linkedlifedata.com/resource/pubmed/chemical/Cyclohexanecarboxylic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Cyclohexenes, http://linkedlifedata.com/resource/pubmed/chemical/Enediynes, http://linkedlifedata.com/resource/pubmed/chemical/Indoles, http://linkedlifedata.com/resource/pubmed/chemical/adozelesin
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Induction of DNA damage responses by adozelesin is S phase-specific and dependent on active replication forks.
pubmed:affiliation
Departments 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.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't