Influence of DNA Ends on Structure and Function of the DNA-dependent Protein Kinase

Hdl Handle:
http://hdl.handle.net/10675.2/317693
Title:
Influence of DNA Ends on Structure and Function of the DNA-dependent Protein Kinase
Authors:
Jovanovic, Marko
Abstract:
Non-homologous end joining is a major DNA double-strand break repair pathway in mammalian cells. The DNA-dependent protein kinase (DNA-PK), consisting of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Ku heterodimer, is hypothesized to be a key regulator of the pathway. Available data suggest DNA-PKcs may exert this regulatory function by controlling access to the DNA termini and by phosphorylation of itself and other proteins. I further characterized DNA-PK-DNA interaction by studying binding of DNA-PKcs and Ku to oligonucleotides with chemically defined end structures under conditions that preclude synapsis between opposing DNA ends. Binding of DNA-PKcs to DNA varied with the end structure in a manner that suggests that partial melting of DNA ends is necessary for the formation of a stable, enzymatically active complex. Unexpectedly, these studies also revealed that ATP, as well as its nonhydrolyzable analog AMP-PNP, have an allosteric effect on the interaction of DNA-PKcs with DNA.
Affiliation:
Institute of Molecular Medicine and Genetics
Issue Date:
Dec-2006
URI:
http://hdl.handle.net/10675.2/317693
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304954908?accountid=12365
Type:
Dissertation
Language:
en
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorJovanovic, Markoen
dc.date.accessioned2014-06-03T02:42:56Z-
dc.date.available2014-06-03T02:42:56Z-
dc.date.issued2006-12-
dc.identifier.urihttp://hdl.handle.net/10675.2/317693-
dc.description.abstractNon-homologous end joining is a major DNA double-strand break repair pathway in mammalian cells. The DNA-dependent protein kinase (DNA-PK), consisting of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Ku heterodimer, is hypothesized to be a key regulator of the pathway. Available data suggest DNA-PKcs may exert this regulatory function by controlling access to the DNA termini and by phosphorylation of itself and other proteins. I further characterized DNA-PK-DNA interaction by studying binding of DNA-PKcs and Ku to oligonucleotides with chemically defined end structures under conditions that preclude synapsis between opposing DNA ends. Binding of DNA-PKcs to DNA varied with the end structure in a manner that suggests that partial melting of DNA ends is necessary for the formation of a stable, enzymatically active complex. Unexpectedly, these studies also revealed that ATP, as well as its nonhydrolyzable analog AMP-PNP, have an allosteric effect on the interaction of DNA-PKcs with DNA.en
dc.language.isoenen
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304954908?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.-
dc.subjectNon-homologous End Joiningen
dc.subjectDNA-dependent Protein Kinaseen
dc.subjectDouble-Strand Break DNA Repairen
dc.subjectDNA-Protein Interactionen
dc.subjectSurface Plasmon Resonanceen
dc.titleInfluence of DNA Ends on Structure and Function of the DNA-dependent Protein Kinaseen
dc.typeDissertationen
dc.contributor.departmentInstitute of Molecular Medicine and Genetics-
dc.description.advisorDynan, William S.en
dc.description.committeePollock, Jennifer S.; Flores-Rozas, Hernan; Phillips, Andrew C.; Yu, Robert K.en
dc.description.degreeDoctor of Philosophy (Ph.D.)-
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