Format

Send to

Choose Destination
DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1057-62.

Constitutively active DNA damage checkpoint pathways as the driving force for the high frequency of p53 mutations in human cancer.

Author information

1
Wistar Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-4268, USA. halazonetis@wistar.upnn.edu

Abstract

If the major function of the p53 protein is to function as a DNA damage checkpoint protein, then it is reasonable to hypothesize that its inactivation in human cancer must be related to its DNA damage checkpoint function. This hypothesis further implies that in tumor cells one or more of the DNA damage checkpoint pathways has been activated. Otherwise, p53 would not be active and there would be no selective pressure for TP53 mutations. I make the argument that tumorigenic transformation is intrinsically associated with formation of DNA DSBs in every cell cycle leading to activation of DNA damage checkpoint pathways. In turn, activation of the DNA DSB checkpoint provides the selective pressure for the high frequency of p53 inactivation in human cancer.

PMID:
15279793
DOI:
10.1016/j.dnarep.2004.03.036
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center