Fatal quality control in oocytes
18th February 2011
Maintaining DNA integrity in oocytes is of paramount importance to avoid dissemination of mutations to the next generation. A tight quality control mechanism exists, which leads to sacrificing oocytes rather than risking any damage. This is especially painful for female cancer patients treated with chemotherapy, as chemotherapeutic agents damage the DNA of oocytes, resulting in cell death and, consequently, in infertility. Little has been known about the exact mechanisms triggering cell death; therefore therapeutic approaches to prevent infertility have remained ineffective.
In cooperation with international partners, the group of FMLS scientist Volker Dötsch has now started to unveil the mechanism behind the treatment related infertility. Essential for this process is the protein p63, a member of the p53 protein family which has gained a reputation as "guardian of the genome". The Dötsch group has now shown how p63 is regulated. In normal oocytes, the level of p63 is high, but the protein is kept in a closed dimeric and inactive state. If DNA is damaged, p63 becomes phosphorylated and the structure of the dimer changes to an open state allowing the attachment of a second phosphorylated dimer. The result is an active p63 tetramer which is capable of initiating cell death of damaged oocytes. Link to full article and German press release.