2026-09-20T08:53:14Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/810332022-01-13T07:53:55Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Paul Chang.
Rood, Jennifer E. (Jennifer Evelyn)
Massachusetts Institute of Technology. Department of Biology.
Massachusetts Institute of Technology. Department of Biology
2013-09-24T19:38:21Z
2013-09-24T19:38:21Z
2013
2013
http://hdl.handle.net/1721.1/81033
857791165
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2013.
Cataloged from PDF version of thesis.
Includes bibliographical references.
The poly(ADP-ribose) polymerase (PARP) family of enzymes in humans is comprised of 17 proteins. PARP-1, the first member of the family, synthesizes a large, complex post-translational modification, poly(ADP-ribose). While PARP-1 and some other PARPs have been extensively functionally characterized, the enzymatic and cellular functions of many PARPs are unknown. This thesis presents work that seeks to characterize the enzymatic functions of the PARP family. First, experimental demonstration of the automodification capacity of each PARP is presented. We find that PARP enzymatic activity largely conforms to bioinformatic predictions of PARP activity. Then, we seek to provide a structural rationale for these enzymatic capabilities based on the analysis of extant and modeled crystal structures of each PARP. We present a structural hypothesis for catalytic differences among PARPs. Finally, we examine methods for the identification of cellular targets of PARP activity and functional interaction partners of PARPs. Together, these elements of PARP characterization will aid in the discovery of physiologically relevant targets and a mechanistic understanding of PARP enzymatic activity in the cellular context.
by Jennifer E. Rood.
Ph.D.
226 p.
eng
Massachusetts Institute of Technology
M.I.T. theses are protected by
copyright. They may be viewed from this source for any purpose, but
reproduction or distribution in any format is prohibited without written
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http://dspace.mit.edu/handle/1721.1/7582
Biology.
Structure and function of the human Poly(ADP-ribose) polymerase enzyme family
Thesis
application/pdf
Publication
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unknown
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<Abstract>The poly(ADP-ribose) polymerase (PARP) family of enzymes in humans is comprised of 17 proteins. PARP-1, the first member of the family, synthesizes a large, complex post-translational modification, poly(ADP-ribose). While PARP-1 and some other PARPs have been extensively functionally characterized, the enzymatic and cellular functions of many PARPs are unknown. This thesis presents work that seeks to characterize the enzymatic functions of the PARP family. First, experimental demonstration of the automodification capacity of each PARP is presented. We find that PARP enzymatic activity largely conforms to bioinformatic predictions of PARP activity. Then, we seek to provide a structural rationale for these enzymatic capabilities based on the analysis of extant and modeled crystal structures of each PARP. We present a structural hypothesis for catalytic differences among PARPs. Finally, we examine methods for the identification of cellular targets of PARP activity and functional interaction partners of PARPs. Together, these elements of PARP characterization will aid in the discovery of physiologically relevant targets and a mechanistic understanding of PARP enzymatic activity in the cellular context.</Abstract>
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