Investigations

Replication stress is one of the major causes for chromosomal instability which is a hallmark of cancer. Incomplete repair can lead to severe mitotic defects and ultra-fine anaphase bridges (UFBs) are a typical consequence. So far, five different classes of UFBs have been discribed: fragile sites-UFBs, centromeric-UFBs, telomeric-UFBs, homologous recombination-UFBs and rDNA-UFBs, which can be distinguished by their location and the way how they arise. Although previous studies have already proposed ...

Genomic instability is a hallmark of cancer and can be frequently induced by replication stress. Incomplete repair of replication intermediates can lead to persistent linkages between sister chromatides, detectable during mitosis as ultra-fine anaphase bridges (UFBs). The active resolution of UFBs via several UFB factors are crucial to prevent mitotic catastrophe, chromosomal missegregations or aneuploidy. Previous studies have already revealed that UFBs are processed by a distinct set of proteins, ...

Many cancer cells are chromosomally unstable, a phenotype describing a tendency for accumulating chromosomal aberrations. Entire chromosomes tend to be gained or lost, which is called whole chromosome instability (W-CIN). Structural chromosomal instability (S-CIN) describes an increased rate of gaining, losing or translocating smaller parts of chromosomes. Here we analyse data from 33 cancer types to find differences and commonalities between W-CIN and S-CIN. We find, that W-CIN is strongly linked ...

Cancer researchers perform experiments with cell lines to better understand the biology of cancer and to develop new anti-cancer treatments. A prerequisite to translate promising results from these \textit{in vitro} experiments to clinical applications is to use the most appropriate cell line for a given tumour or cancer subtype. We present MFmap (model fidelity map), a deep learning technique to integrate cancer genomic data from patients with cell line data. The MFmap neural network compresses ...

Chromosomal instability (CIN) is a hallmark of cancer and comprises structural (S-CIN) and numerical CIN (W-CIN). Recent work indicated that replication stress (RS), known to contribute to S-CIN, also affects mitotic chromosome segregation, thereby possibly explaining the common co-existence of S-CIN and W-CIN in human cancer. Here, we show that RS-induced dormant origin firing is sufficient to trigger W-CIN in human cancer cells. We discovered that overexpression of origin firing genes including ...

Whole chromosome instability (W-CIN) is a hallmark of human cancer and contributes to the evolvement of aneuploidy. W-CIN can be induced by abnormally increased microtubule plus end assembly rates during mitosis leading to the generation of lagging chromosomes during anaphase as a major form of mitotic errors in human cancer cells. Here, we show that loss of the tumor suppressor genes TP53 and TP73 can trigger increased mitotic microtubule assembly rates, lagging chromosomes and W-CIN. CDKN1A, ...

Chromosomal instability (CIN) causes structural and numerical chromosome aberrations and represents a hallmark of cancer. Replication stress (RS) has emerged as a driver for structural chromosome aberrations while mitotic defects can cause whole chromosome missegregation and aneuploidy. Recently, first evidence indicated that RS can also influence chromosome segregation in cancer cells exhibiting CIN, but the underlying mechanisms remain unknown. Here, we show that chromosomally unstable cancer ...