Abstract
Simple SummaryChromosomal instability (CIN), a condition in which chromosome missegregation occurs at high rates, is widely seen in cancer cells. Causes of CIN in cancer cells are not fully understood. A recent report suggests that chromosome oscillation, an iterative chromosome motion typically seen in metaphase around the spindle equator, is attenuated in cancer cells, and is associated with CIN. Chromosome oscillation promotes the correction of erroneous kinetochore-microtubule attachments through phosphorylation of Hec1, a kinetochore protein that binds to microtubules, by Aurora A kinase residing on the spindle. In this review, we focused on this unappreciated link between chromosome oscillation and CIN.Chromosomal instability (CIN) is commonly seen in cancer cells, and related to tumor progression and poor prognosis. Among the causes of CIN, insufficient correction of erroneous kinetochore (KT)-microtubule (MT) attachments plays pivotal roles in various situations. In this review, we focused on the previously unappreciated role of chromosome oscillation in the correction of erroneous KT-MT attachments, and its relevance to the etiology of CIN. First, we provided an overview of the error correction mechanisms for KT-MT attachments, especially the role of Aurora kinases in error correction by phosphorylating Hec1, which connects MT to KT. Next, we explained chromosome oscillation and its underlying mechanisms. Then we introduced how chromosome oscillation is involved in the error correction of KT-MT attachments, based on recent findings. Chromosome oscillation has been shown to promote Hec1 phosphorylation by Aurora A which localizes to the spindle. Finally, we discussed the link between attenuated chromosome oscillation and CIN in cancer cells. This link underscores the role of chromosome dynamics in mitotic fidelity, and the mutual relationship between defective chromosome dynamics and CIN in cancer cells that can be a target for cancer therapy.
Highlights
Most cancer cells have an abnormal number and structure of chromosomes [1,2]
A recent report suggests that Cdk1, a main kinase reported that Chk1, which phosphorylates and activates Aurora B [105], is involved important for mitotic progression, phosphorylates the Hec1 tail, which may be involved in error correction
A recent report suggests another possibility that chromosome oscillation contributes to the correction of erroneous KT-MT attachments [147]
Summary
Most cancer cells have an abnormal number and structure of chromosomes [1,2]. Gain or loss of entire chromosomes is called (whole chromosome) aneuploidy, while amplification or loss of parts of chromosomes is called structural (or segmental) aneuploidy [3,4,5]. Aneuploid cancer cells exhibit increased rates of chromosome missegregation, which is called chromosomal instability (CIN) [7,8,9]. Proper attachment of a kinetochore (KT), a proteinous structure formed at the centromeric region on a chromosome, to spindle microtubules (MTs) is a prerequisite for faithful chromosome segregation. MTs are cylindrical assembly of protofilaments formed by heterodimers of α and β tubulin This structure stochastically repeats elongation (by polymerization of tubulin heterodimers) and shrinkage (by depolymerization of tubulin heterodimers), a phenomenon known as dynamic instability that facilitates attachment to KTs [15]. We introduce a previously unappreciated link between chromosome oscillation and error correction mechanism, and describe attenuated chromosome oscillation as a novel cause of CIN in cancer cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
