Strategic Communication and Public Relations

Alternate ending – living on without telomerase

No. 58 | 03/11/2011 | by Koh

Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have discovered an alternative mechanism for the extension of the telomere repeat sequence by DNA repair enzymes.

In some cancer cells, APB complexes (yellow) induce the extension of the telomere repeats (red).
© dkfz.de

The ends of the chromosomes, the telomeres, are repetitive DNA sequences that shorten every time a cell divides during the process of duplicating its genome. Once the telomeres become very short the cell stops dividing. Thus, telomeres work like a cellular clock that keeps an eye on the number of cell divisions. And once the cell’s time is over it can no longer divide. Circumventing this control mechanism is crucial for tumor cells in order to proliferate without limits. In the majority of tumors this is accomplished by reactivating telomerase, an enzyme that normally extends the telomeres only in embryonic cells, and thus resets the cellular clock during development. However, a 10-15% fraction of tumors keeps on dividing without telomerase by making use of what is called the ALT-mechanism for “Alternative Lengthening of Telomeres”. The hallmark of ALT cancer cells is a special type of complexes of promyelocytic leukemia (PML) protein at the telomeres that are termed ALT-associated PML nuclear bodies or APBs.

ALT-tumors can be identified by the presence of APBs on fluorescence microscopy images since normal cells do not have these structures. However, the function of APBs has remained mysterious. In a recent study, Inn Chung and Karsten Rippe from the German Cancer Research Center together with Heinrich Leonhard from the LMU in Munich applied a novel approach to study APBs. They succeeded in artificially making APBs in living cells by tethering PML and other APB proteins to the telomeres. In this manner they could not only trace the assembly of APBs but were able to investigate what happens after APB formation. They could show that the de novo formed APBs induced the extension of the telomere repeat sequence by a DNA repair synthesis mechanism. This demonstrates for the first time that APBs have an important function for the alternative telomere lengthening mechanism, and suggests that disrupting APBs would stop proliferation of ALT-positive tumor cells once their telomeres become too short. This makes APBs a promising new target of cancer cells, in which the ALT mechanism is active.

Publication: Chung, I., Leonhardt, H. & Rippe, K. (2011). De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation. J. Cell Sci., doi: 10.1242/jcs.084681.

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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