Structure and function of the human Poly(ADP-ribose) polymerase enzyme family

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2013

Author dc:creator

• Rood, Jennifer E. (Jennifer Evelyn)

Advisor dc:contributor.advisor

• Paul Chang.

• Biology.

Statement dc:rights

• 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 permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/81033

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/81033