BMP-smad pathway in DNA damage response
Gan, Hwee Yee
Date of Issue2009
School of Chemical and Biomedical Engineering
A*STAR Institute of Molecular and Cell Biology
DNA damage response is a mechanism that can prevents cancer development. In DNA damage response, ATM-p53 pathway is one of the pathways activated to induce DNA repair, cell cycle arrest and apoptosis which ultimately prevent tumorgenesis. Recent genetic studies have revealed that BMP-Smad pathway has a function that suppresses tumorgenesis. An inactivation of this pathway leads to tumorigenesis in both human and mouse. However, their interaction is still a mystery because BMP-Smad pathway is a complex pathway. Previous studies have shown that deficiency of p53 gene leads to activation of BMP-Smad pathway. Hence, in this project, DNA damage proteins (p53 and ATM) were used to test the effect of Smad1 whether there is a possible link between ATM-p53 and BMP-Smad pathway. The experiment findings have shown that elevation of Smad1 plays similar role as p53 in DNA damage response, cell transformation and tumorigenesis. Furthermore, Smad1 appears to up-regulate when p53 and ATM are deficient. Hence, a failure in ATM-p53 pathway activates the BMP-Smad1 pathway which may serve as a compensatory mechanism. This study and the results obtained establish that BMP-Smad1 signaling is an integral part of DNA damage response.
Final Year Project (FYP)
Nanyang Technological University