Login

Publications  •  Project Statistics

Glossary  •  Schools  •  Disciplines
People Search: 
   
Title/Abstract Search: 

Dissertation Information for Bahrad Ali Sokhansanj

NAME:
- Bahrad Ali Sokhansanj

DEGREE:
- Ph.D.

DISCIPLINE:
- Engineering

SCHOOL:
- University of California, Davis (USA) (2002)

ADVISORS:
- None

COMMITTEE MEMBERS:
- None

MPACT Status: Incomplete - Not_Inspected

Title: Mathematical models of human DNA base excision repair

Abstract: "The DNA in human cells is constantly being damaged by a combination of endogenous sources, such as spontaneous hydrolysis of bases and reactive oxygen species produced by cellular metabolism, and external causes, such as toxins and ionizing radiation. If not repaired, damaged DNA can result in cell death or mutagenesis, which potentially leads to cancer and disease. Thus, cells have evolved efficient mechanisms to repair different kinds of damage to DNA, including base excision repair (BER), which repairs single damaged sites (such as an oxidized base or abasic site). The human BER pathway is a multistep process involving the sequential activity of several proteins. Based on epidemiological and molecular data, it has been hypothesized that genetic variation in one or more BER proteins results in reduced capacity to repair DNA, leading to increased susceptibility to cancer and other disease caused by DNA damage.

Traditional graphical and linguistic models of biology can not be used to accurately study the complex interaction and evaluate the differential impact of normal and variant BER proteins. Thus, quantitative kinetic data on single proteins of BER have been used here to develop a mathematical model of the BER pathway, using ordinary differential equations derived for enzyme kinetics. The BER model is used to obtain mechanistic insight and predict the effect of variation in BER proteins. Key mechanistic results include support for previously described hypotheses of cooperativity between apurinic/apyrimidinic (AP) endonuclease (Ape1) and 8-oxoguanine DNA glycosylase (Ogg1), and between Ape1 and polymerase β (Polβ), as well as agreement with previous data indicating that Polβ activity is key to determining overall BER capacity in vitro . The model predicts, however, that while critical for BER function, Ape1 kinetics and concentration do not determine overall BER capacity under most conditions. Modeling also predicts coordination between the two distinct activities of Polβ, and suggests a key role for ""baton passing"" mechanisms and overall pathway coordination between all BER proteins. The BER model and simulation results described here represent an important first step towards developing a predictive facility for genotype-based evaluation of the individual risk of exposure to DNA damaging agents."

MPACT Scores for Bahrad Ali Sokhansanj

A = 0
C = 1
A+C = 1
T = 0
G = 0
W = 0
TD = 0
TA = 0
calculated 2008-01-31 06:30:28

Advisors and Advisees Graph

generating graph, please reload

Students under Bahrad Ali Sokhansanj

ADVISEES:
- None

COMMITTEESHIPS:
- Illhoi Yoo - Drexel University (2006)