Georgia Southern University
MSH2 nuclear localization and MMR apoptotic response to DNA damage.
Abstract
dc:description.abstract<p>Mismatch repair (MMR) proteins have previously been implicated to play a role in cellular apoptotic response to chemotherapeutics. However, what has not been established is how these proteins participate in both repair events and apoptosis. We are here investigating if cellular compartmentalization of disparate MMR functions plays a role in orchestrating these two opposite responses to DNA damage. Initial data from our lab and others indicated that MMR proteins can participate in apoptosis via a repair-dependent and -independent mechanism, dependent on the type of damage. Nuclear influx of MSH2 may be part of the repair-independent mechanism. Results from confocal microscopy and fluorescent linked immunosorbent assays showed both a corollary movement of MSH2 with the MMR repair protein EXO1, as well as an ability of the two proteins to bind with one another. Caspase-3 assay’s conducted on cells treated with either the intrastrand crosslink drug Cisplatin or the frameshift mutation drug ICR191 showed that only cells with normal expression of MSH2 and EXO1 as well as those cells treated with Cisplatin showed a significant apoptotic response above the control. These data suggest that EXO1 plays a role in MSH2’s movement into the nucleus when treated with a drug that induces apoptosis, and that the switch between repair and repair-independent apoptotic response may be aided by cellular compartmentalization.</p>
Degree
thesis:*- Name thesis:degree_name
- Master of Science in Biology (M.S.)
- Level thesis:degree_level
- Thesis (restricted to Georgia Southern)
- Discipline thesis:degree_discipline
- Department of Biology
- Year dc:date.available
- 2014
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Jarzen, John D
- Contributors dc:contributor
-
- Johanne Lewis
- Marina Eremeeva
Subjects
dc:subject × 7Identifiers
dc:identifier.*- Repository record dc:identifier
- https://digitalcommons.georgiasouthern.edu/etd/1111
- OAI identifier oai:identifier
- oai:digitalcommons.georgiasouthern.edu:etd-2160