Projects

We intend to shed light on the interplay between the regulation of replication origin firing and mitotic chromosome segregation. The relationship between faithful genome replication and chromosome segregation is mutual: de-regulated genome replication causes replication stress and chromosome missegregation [1, 2]. Conversely, chromosome missegregation causes replication stress [3, 4]. Although it is clear that proper regulation of origin firing, the main focus of our lab, is key for complete and ...

To maintain genome stability, human cells depend on accurate DNA replication in S-phase and chromosome segregation in mitosis. Replication stress refers to slowing down or stalling of replication forks that occurs due to DNA lesions, R-loops or oncogene activation. One consequence of replication stress is entry of cells into mitosis with incompletely replicated DNA and thus aberrant mitosis. Phosphorylation of proteins by kinase ATR and its downstream effector CHK1 protects stalled replication ...

Structural and numerical chromosome aberrations are commonly and concomitantly detected in cancer and in age-related syndrome cells suggesting a functional relationship between structural and whole chromosome instability (S-CIN and W-CIN, respectively). Recent evidence suggests that replication stress can not only drive S-CIN and the generation of structural chromosome aberrations, but might also be involved in W-CIN leading to whole chromosome missegregation during mitosis resulting in aneuploidy. ...

Test

Replication stress (RS) and chromosomal instability (CIN) are commonly observed features of cancer cells. RS has a destabilizing effect on the genome and, vice versa, whole chromosome aneuploidy as a result of CIN can induce a RS response. Our preliminary data analysis of cancer genomic data suggests a tendency of whole chromosome CIN (W-CIN) to co-occur with structural CIN (S-CIN), whilst S-CIN can also appear in numerical stable tumors. We also found a significant positive correlation of mRNA ...