Chromosome instability and kinetochore dysfunction.
Chromosomal instability (CIN) has been recognized as a hallmark of human cancer and is caused by continuous chromosome missegregation during mitosis. Proper chromosome segregation requires a physical connection between spindle microtubules and centromeric DNA and this attachment occurs at proteinaceous structures called kinetochore. Thus, defect in kinetochore function is a candidate source for CIN and the generation of aneuploidy. Recently, a number of kinetochore components have been shown to be mutated and/or aberrantly expressed in human cancers, which suggests an important role of kinetochore for CIN and carcinogenesis. In this article, we will discuss about how kinetochore dysfunction causes CIN and might lead to the development of cancer.
Tomonaga
T
T
Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan. Tomonaga@faculty.chiba-u.jp
Nomura
F
F
D043171:Chromosomal Instability; D006801:Humans; D018386:Kinetochores / Q000473:pathology*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*