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Title page for ETD etd-03252014-150303

Type of Document Dissertation
Author Couch, Frank Benjamin IV
URN etd-03252014-150303
Title Regulation of Stalled Replication Forks by ATR
Degree PhD
Department Biochemistry
Advisory Committee
Advisor Name Title
David Cortez Committee Chair
Brandt F. Eichman Committee Member
Bruce D. Carter Committee Member
Christine M. Eischen Committee Member
Scott W. Hiebert Committee Member
  • cell cycle checkpoint
  • replication stress
  • DNA replication
  • DNA damage response
  • ATR
Date of Defense 2014-03-14
Availability unrestricted
Errors during DNA replication lead to mutations which contribute to cancer development. To deal with these challenges, cells contain an innate machinery known as the replication stress response. ATR is the master regulator of the replication stress response, and much is known about ATR signaling. However, it is unclear how ATR signaling promotes replication fork repair and prevents pathogenic replication fork processing. In this dissertation, I conducted several studies of the replication stress response to stalled forks. I characterized the protein recruitment and post-translational modifications that occur at replication forks in response to damage using the iPOND methodology. I demonstrated that ATR phosphorylates SMARCAL1 to prevent replication fork collapse. Finally, I began an investigation into the biochemical mechanism by which SMARCAL1 and the related annealing helicases, ZRANB3, UvsW, and RecG, perform fork regression.
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  Couch-Dissertation-FINAL-20140325.pdf 30.42 Mb 02:20:49 01:12:25 01:03:22 00:31:41 00:02:42

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