Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/16056
Title: | CHARACTERIZATION OF MUTL-MEDIATED PROTEIN INTERACTIONS IN DNA MISMATCH REPAIR |
Authors: | Pillon, Monica |
Advisor: | Guarne, Alba |
Department: | Biochemistry and Biomedical Sciences |
Keywords: | Mismatch repair;MutL;MutS;sliding clamp |
Abstract: | DNA encodes the genetic information of the cell, therefore, every single living organism has a precise DNA damage response mechanism to safeguard DNA integrity. Base mismatches are endogenous DNA lesions introduced by the replicative polymerase during DNA replication. The conserved DNA mismatch repair pathway corrects these base mismatches. Mismatch repair initiation is orchestrated by two proteins, MutS and MutL. MutS recognizes and binds to base mismatches and relays the presence of the lesion to MutL. MutL, in turn, interacts with downstream factors to coordinate mismatch excision. The processivity clamp, typically known for its role in tethering the DNA polymerase to DNA during replication, is also involved in several steps of this repair process including MutL endonuclease activation and strand resynthesis. The dynamics of the MutS-MutL and MutL-processivity clamp interactions present one of the bottlenecks to uncovering the spatial and time organization of these protein assemblies. Therefore, little is known about the interactions that orchestrate the early steps of mismatch repair. The biochemical and structural work included in this thesis outlines a precise series of molecular cues that activate MutL. |
URI: | http://hdl.handle.net/11375/16056 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Monica Pillon PhD Thesis--final.pdf | PhD Thesis - DNA Mismatch Repair | 9.75 MB | Adobe PDF | View/Open |
Movie S2.1.mov | Movie S2.1 | 7.46 MB | Video Quicktime | View/Open |
Movie S5.1.mp4 | Movie S5.1 | 2.39 MB | Unknown | View/Open |
Movie S5.2.mp4 | Movie S5.2 | 1.47 MB | Unknown | View/Open |
Movie S5.3.mp4 | Movie S5.3 | 2.91 MB | Unknown | View/Open |
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