ATM and CHK-1 activity in young versus senescent human fibroblasts
Date
2006
Authors
Axelrad, Jessica D., author
Ray, Andrew F., author
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Abstract
ATM and CHK1 are two different DNA repair proteins. As such, they are an important factor in preventing tumors caused by multiple damages and subsequent mutations in the DNA strands. As people get older they have an increased chance of getting cancer because their cells have had more opportunities to mutate. We hypothesized that it is also possible a person's chance of getting cancer increases with age because the DNA repair proteins, such as ATM and CHK1, become less efficient with age. Protein activity was evaluated by first damaging cellular DNA in young, middle aged, and senescent human fibroblasts, by exposing them to gamma radiation. A Western blot analysis was then performed to determine the concentration of phosphorylated (or activated) ATM and CHK1 proteins in these different aged cells. The data showed that the ATM proteins become more phosphorylated the more radiation the cells are exposed to (as expected), but that, especially in the 10-G cells, the young and middle aged cells have a higher concentration of activated ATM than the old cells. There is a similar pattern with the CHK1 protein blot. The activated protein concentration increases with an increased dose of radiation, but while the 10-G young and middle aged cells have a significant CHK1 concentration, the near senescent cells do not. This decrease in DNA repair protein activation contributes to a person's increased likelihood of cancer. Not only have the older cells undergone more opportunities for a genetic mutation to occur, but the ability of the cell to repair DNA damage appears to be compromised. Future studies will include DNA repair assays.
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Subject
DNA repair
Fibroblasts
Cancer