Approval Sheet Single-molecule Studies of DNA Mismatch Recognition Público
Coats, Julie Ellen (2012)
Published
Abstract
Single-molecule Studies of DNA
Mismatch Recognition
The DNA mismatch repair system protects the genome from
spontaneous
mutations by recognizing and repairing DNA synthesis errors in a
pathway that is highly
conserved. The MutS family of proteins initiate DNA mismatch repair
by specifically
binding mismatched or extrahelical bases and communicating the
presence of damage to
downstream repair proteins in an ATP-dependent manner. Previous
structural studies
have implied that MutS-induced conformational changes on DNA are
central to damage
recognition. Because the conformational changes occur on the
timescale of seconds, it is
difficult to obtain kinetic information on this highly dynamic
process with traditional
ensemble techniques. In this work, we use single-molecule
fluorescence resonance
energy transfer to investigate the conformational dynamics of
mismatched DNA
substrates in the absence and presence of DNA mismatch recognition
proteins. We
present quantitative kinetic information on the dynamics of DNA
substrates and on the
rates of MutS binding and dissociation in a variety of buffer
conditions.
Mismatch Recognition
B.A., Hendrix College, 2006
Advisor: Ivan Rasnik, Ph.D.
A dissertation submitted to the Faculty of the James T. Laney
School of Graduate Studies
of Emory University in partial fulfillment of the requirements for
the degree of Doctor of
Philosophy in Physics
2012
Table of Contents
Table of Contents
Chapter 1:
Introduction
...………………………………………………………………
1
Figure 1.1
………………………………………………………………………..10
Table 1.1
………………………………………………………………………..
11
Chapter 2: Single-molecule fluorescence resonance energy
transfer ………………... 12
Figure 2.1
……………………………………………………………………….
28
Figure 2.2
……………………………………………………………………….
28
Figure 2.3
……………………………………………………………………….
29
Figure 2.4
……………………………………………………………………….
30
Figure 2.5
……………………………………………………………………….
30
Figure 2.6
……………………………………………………………………….
31
Figure 2.7
………………………………………………………………………..32
Chapter 3: Discrete conformational dynamics in three-way DNA
junctions ...……… 33
Figure 3.1
……………………………………………………………………….
52
Figure 3.2
……………………………………………………………………….
53
Figure 3.3
……………………………………………………………………….
54
Figure 3.4
……………………………………………………………………….
55
Figure 3.5
……………………………………………………………………….
56
Figure 3.6
……………………………………………………………………….
57
Figure 3.7
………………………………………………………………………..58
Figure 3.8
………………………………………………………………………..59
Figure 3.9
………………………………………………………………………..60
Conformational trapping of Human Mismatch Recognition
Complex
MSH2/MSH3 on repair-resistant DNA
loops……………………………..
61
Figure 4.1
……………………………………………………………………….
83
Table 4.1
………………………………………………………………………..
84
Table 4.2
………………………………………………………………………..
84
Figure 4.2
……………………………………………………………………….
85
Figure 4.3
……………………………………………………………………….
86
Figure 4.4
……………………………………………………………………….
87
Figure 4.5
……………………………………………………………………….
88
Figure 4.6
……………………………………………………………………….
89
Figure 4.7
………………………………………………………………………..90
Figure 4.8
………………………………………………………………………..91
Table 4.3
………………………………………………………………………..
92
Table 4.4
………………………………………………………………………..
92
Figure 4.9
………………………………………………………………………..93
Figure 4.10
……………………………………………………………………...
94
Figure 4.11
……………………………………………………………………...
95
Chapter 5: The binding kinetics of E. coli MutS
influence DNA mismatch
selectivity………………………………………………………………….
96
Figure 5.1
……………………………………………………………………...
112
Figure 5.2
………………………………………………………………………113
Figure 5.3
………………………………………………………………………114
Figure 5.4
………………………………………………………………………115
About this Dissertation
School | |
---|---|
Department | |
Degree | |
Submission | |
Language |
|
Research Field | |
Palabra Clave | |
Committee Chair / Thesis Advisor | |
Committee Members |
Primary PDF
Thumbnail | Title | Date Uploaded | Actions |
---|---|---|---|
|
Approval Sheet Single-molecule Studies of DNA Mismatch Recognition () | 2018-08-28 16:31:47 -0400 |
|
Supplemental Files
Thumbnail | Title | Date Uploaded | Actions |
---|