Inhibiting tumour-specific repair mechanisms
Research group at TU Darmstadt with „Nature“ publication
2021/10/14
Mutations of the BRCA1 and BRCA2 genes – also known as “breast cancer genes” – are associated with the development of inherited breast cancer as well as other types of tumours. A group of researchers from the Technical University of Darmstadt, the University of California and the University of Texas, characterized the specific repair processes in BRCA2-mutated tumour cells providing findings that can help to develop new or to improve existing strategies in cancer therapy. The results of this study were recently published in the renowned science journal Nature Cell Biology (NCB).
The DNA which encodes the genetic information of each cell is constantly damaged by endogenous and exogenous influences. The thousands of DNA lesions arising every day in each cell of our body are effectively detected and repaired by different cellular mechanisms called the DNA damage response. Defects of these mechanisms can be associated with cancer development.
The most severe DNA lesion is the DNA double-strand break as the DNA molecule is completely raptured. One double-strand break can already be sufficient to kill a cell if it stays unrepaired or if it is repaired in an error-prone manner. Homologous recombination is one of two main repair pathways for repairing double-strand breaks and BRCA1 and BRCA2 genes are essential for this process. Thus, this repair pathway is defective in tumour cells harbouring mutations for BRCA1 or BRCA2.
The research group of Professor Markus Löbrich at TU Darmstadt has characterized a specific alternative repair process in BRCA2-mutated cells. This study was recently published in the renowned science journal Nature Cell Biology. Together with research groups of the University of California and the University of Texas, Löbrich and colleagues demonstrate that a repair process called POLθ-mediated end-joining (TMEJ) is responsible for repairing double-strand breaks in BRCA2-mutated cells.