Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.
Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.
Date of Award
Doctor of Philosophy (PhD)
Damage to actively transcribed genes is repaired at a faster rate than damage to non-transcribed genes due to the activity of proteins called transcription repair coupling factors. These proteins recognize RNA polymerases that have stalled on damaged DNA, remove them, and recruit DNA repair proteins to the site of the damage. In bacteria one protein performs all of those functions, Mfd. We are investigating the regulation of Mfd's activity and we hypothesize that the opening and closing of the interface between the protein's two principal domains, Mfd N (residues 1-450) and MfdC (residues 473-1148), toggles Mfd between active and inactive states. We have solved the crystal structure of MfdN by molecular replacement. Its structure superimposes well with that same region from the crystal structure of the full length Mfd protein (Deaconescu et al 2006), with an rmsd of 1.1 Å. The fold of MfdN appears to be independent of MfdC and the linker region (451-472), which is too disordered to be seen in the crystal structure. We have probed the stability of the N and C terminal regions of Mfd expressed as separate constructs, and the effect of disrupting the interface between them on the properties of Mfd. We believe that Mfd N exerts a stabilizing influence on structure of full length Mfd, and that it has an inhibitory effect on the protein's activity through its binding interactions with MfdC .
Murphy, Michael N, "Structure Of MFDn And Its Influence On The Stability And Activity Of The MFD Protein" (2009). Doctoral Dissertations 1896 - February 2014. 57.