This news release is available in German.
DNA - the carrier of genetic information - is constantly threatened by damage originating from exogenous and endogenous sources. Very special DNA lesions are DNA-protein crosslinks - proteins covalently linked to DNA. So far hardly anything was known about repair mechanisms specifically targeting DNA-protein crosslinks. Stefan Jentsch's team at the Max Planck Institute of Biochemistry in Martinsried, Germany, now discovered a protease that is able to chop down the protein component of DNA-protein crosslinks, thereby enabling organisms to copy their genetic information even if crosslinks arise. The results of this study have major implications for the understanding of genome integrity and cancer development.
The DNA in each cell is highly vulnerable to various types of damage. A special class of damage is caused by reactive compounds, such as formaldehyde, which are produced as byproducts of cellular reactions and cause the crosslinking (a formation of a covalent linkage) of proteins to DNA. Importantly, these so-called DNA-protein crosslinks are also caused by several anti-cancer drugs and are extremely toxic as they interfere with essential processes such as DNA replication. Cells need to unwind and separate the DNA double helix in order to copy its genetic information prior to the next round of cell division. DPCs inhibit this process by blocking the way of the unwinding enzyme replicative helicase, thus preventing replication and consequently cell division.
In the laboratory of Stefan Jentsch at the Max-Planck-Institute of Biochemistry, scientists now identified the protease Wss1 as a new safeguarding factor that chops down the protein components of DNA-protein crosslinks and thereby enables cells to duplicate the
|Contact: Dr. Stefan Jentsch|