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Why chemotherapy causes more infertility in women than in men
Date:2/22/2011

c state the tumor suppressor is active and initiates either repair of the damaged DNA or programmed cell death. Surprisingly, despite the fact that p53 and p63 show high similarity, the mechanism by which the activity of p63 is controlled in oocytes seemed to be different.

The research group of Prof. Volker Dtsch could show now that the two mechanisms that regulate the activity of p53 and of p63 are closely related, but distinct. The level of p63 in normal oocytes is high and the protein is kept in a closed dimeric and inactive state. If DNA double-strand breaks occur, for example caused by radioactive radiation, p63 becomes phosphorylated. As a result of this phosphorylation, the structure of the p63 dimer changes to an open state allowing the attachment of a second phosphorylated dimer. The resulting active p63 tetramer is similar to the active p53 tetramer and leads to the death of the damaged oocyte. Many of the chemotherapeutic agents cause DNA double-strand breaks which activate p63, finally leading to the cell death of the oocytes.

The related proteins of model organisms such as Caenorhabditis elegans (nematode) are also investigated by the Dtsch group. Because of the short life span of this worm its p63 related protein does not act as a tumor suppressor but controls the genetic stability of the germ cells. The quality control of germ cells, thus, seems to be the original function of the p53 protein family and leads to the conclusion that p63 is the ancestor of the entire p53 family.

Interestingly, p63 shows an additional function: it is essential for the maintenance of stem cells in epithelial layers like skin. Because of the close similarity of stem and germ cells, this second function shows the evolutionary process of the p53 protein family from p63-like proteins, that in simple organisms are responsible for the genetic stability of germ cells, via controlling the maintenance of stem cells in organisms with renewal tissues, finally to p53-lik
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Contact: Prof. Volker Doetsch
vdoetsch@em.uni-frankfurt.de
49-697-982-9631
Goethe University Frankfurt
Source:Eurekalert

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