Title page for ETD etd-12162004-112420


Type of Document Master's Thesis
Author Dravid, Amit
Author's Email Address adravid@vt.edu
URN etd-12162004-112420
Title A model of the checkpoint response of the cell cycle of frog-egg extracts in the presence of unreplicated DNA.
Degree Master of Science
Department Mathematics
Advisory Committee
Advisor Name Title
Tyson, John J. Committee Chair
Herdman, Terry L. Committee Co-Chair
Borggaard, Jeffrey T. Committee Member
Sible, Jill C. Committee Member
Keywords
  • cell cycle
  • checkpoint
  • unreplicated DNA
  • ordinary differential equations
  • Chk1
  • wiring diagram
  • computational modeling
  • frog egg extracts
Date of Defense 2004-12-09
Availability unrestricted
Abstract
The cell cycle of eukaryotes consists of alternation between growth and DNA replication (interphase), and DNA distribution and cell-division (mitosis or M-phase). This process is regulated by a complex network of biochemical reactions. A core part of this network, called the "Cell Cycle engine" is evolutionarily conserved. The dimer of CDK1 (a protein kinase) and Cyclin proteins (the regulatory components), called M-phase Promoting Factor (MPF), and its key regulatory proteins Cdc25 and Wee1, are central parts of this cell cycle engine. Maintaining the fidelity of the DNA during the cell cycle is critical for successful propagation of the cell lineage. In the presence of unreplicated DNA, the cell cycle engine''s progress into mitosis is slowed down (or halted) by regulation of MPF activity through Cdc25 and Wee1. This regulatory event, called the unreplicated DNA checkpoint, was modeled in a rudimentary fashion in the Novak and Tyson (1993) model of frog eggs. Since then, many new experiments have uncovered relevant parts of this network. Here, we include these parts into a detailed model of the unreplicated DNA checkpoint in the cell cycle of frog-egg extracts. This work and future studies of the unreplicated DNA checkpoint will lead to its better understanding and hopefully to some strategies for tackling cancer.

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