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Title page for ETD etd-08242011-093413


Type of Document Dissertation
Author Liu, Yang
Author's Email Address y.liu@vanderbilt.edu
URN etd-08242011-093413
Title Pro-apoptotic BID facilitates ATR function following replicative stress
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Kathleen L. Gould Committee Chair
David Cortez Committee Member
Elizabeth Yang Committee Member
Laura A. Lee Committee Member
Sandra S. Zinkel Committee Member
Keywords
  • apoptosis
  • DNA damage
  • RPA
  • ATR/ATRIP
  • BID
  • replicative stress
Date of Defense 2011-08-17
Availability unrestricted
Abstract
First identified as a pro-apoptotic member in the programmed cell death pathway, BH3 interacting domain death agonist (BID) has recently been demonstrated to play a role to maintain genomic integrity and execute DNA damage checkpoints following DNA damage treatments. To clarify the function of BID in the cellular response to DNA damage, especially the response to replicative stress induced DNA damage, I used genetic and biochemical tools to investigate the function and mechanism of BID in the Ataxia-telangiectasia mutated and RAD3-related (ATR)-mediated signaling pathways in this dissertation. BID is demonstrated to mediate the ATR-directed DNA damage response following replicative stress. BID interacts with ATR/ATRIP and RPA to facilitate ATR function in the DNA damage sensor complex. In a mouse model, Bid preserves the hematopoietic system following hydroxyurea-induced replicative stress. Overall, my studies demonstrate the function of BID in the ATR-mediated DNA damage pathway at multiple levels, including protein-protein interaction, signaling transduction, cell function, and animal model. The significance of the dual functions of BID in both DNA damage and cell death pathways will be discussed.
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