Coordination Funds

研究单元2800 （FOR 2800/2）解决了关于染色体不稳定性（CIN）起源的科学问题，这导致了结构和数量染色体畸变。众所周知，CIN和染色体畸变水平升高与许多人类疾病密切相关，包括癌症、神经退行性疾病和年龄相关综合征，并可作为疾病发生和进展的关键驱动因素。导致结构性染色体不稳定（S- cin）并导致结构性染色体畸变的一个重要细胞条件是“复制应激”，其特征是在细胞周期的S期DNA复制过程中复制分叉的缓慢或异常进展。另一方面，有丝分裂过程中的错误导致染色体错误分离是众所周知的全染色体不稳定性（W-CIN）的原因，导致非整倍体的诱导和进化。由于S-CIN和W-CIN经常（如果不是总是）在包括癌症在内的各种cin相关疾病中同时检测到，这两种形式的染色体不稳定性可能在机制上相互关联。事实上，最近的证据表明，复制胁迫可以促进有丝分裂染色体错分离和非整倍体。反之，全染色体非整倍性也会导致复制应激，从而在DNA复制应激和有丝分裂功能障碍之间形成恶性循环。FOR 2800结合了复制胁迫、有丝分裂染色体分离、基因组不稳定性和非整倍性方面的互补科学专业知识，阐明了s期DNA复制胁迫与有丝分裂期间染色体分离紊乱之间的机制联系，反之亦然。2800研究单元的中心目标是定义和描述连接结构和数量染色体不稳定性的分子机制，这是人类疾病和衰老过程的关键驱动因素。

The Research Unit 2800 (FOR 2800/2) addresses the scientific question regarding the origin of chromosome instability (CIN), which causes structural as well as numerical chromosome aberrations. It is well established that CIN and increased levels of chromosome aberrations are closely associated with many human diseases including cancer, neurodegenerative diseases and age-related syndromes and can act as key drivers for disease development and progression. An important cellular condition that causes structural chromosome instability (S-CIN) and leading to structural chromosome aberrations is “replication stress”, which is characterized by a slowed-down or aberrant progression of replication forks during DNA replication in S phase of the cell cycle. On the other hand, errors during mitosis that result in chromosome missegregation are well-known causes of whole chromosome instability (W-CIN) leading to the induction and evolvement of aneuploidy. Since S-CIN and W-CIN are often, if not always, detected concomitantly in various CIN-associated diseases including cancer, the two forms of chromosomal instability might be mechanistically interlinked. In fact, recent evidence indicate that replication stress can promote mitotic chromosome missegregation and aneuploidy. Vice versa, whole chromosome aneuploidy can also contribute to replication stress, thereby establishing a vicious cycle between DNA replication stress and mitotic dysfunction. The FOR 2800 combines complementary scientific expertise on replication stress, mitotic chromosome segregation, genome instability and aneuploidy to elucidate the mechanistic links between DNA replication stress in S-phase and perturbed chromosome segregation during mitosis and vice versa. The central goal of the research unit 2800 is to define and characterize the molecular mechanisms linking structural and numerical chromosome instability, which are key drivers of human diseases and aging processes.