Merotelic kinetochore orientation, aneuploidy, and cancer.
Accurate chromosome segregation in mitosis is crucial to maintain a diploid chromosome number. A majority of cancer cells are aneuploid and chromosomally unstable, i.e. they tend to gain and lose chromosomes at each mitotic division. Chromosome mis-segregation can arise when cells progress through mitosis with mis-attached kinetochores. Merotelic kinetochore orientation, a type of mis-attachment in which a single kinetochore binds microtubules from two spindle poles rather than just one, can represent a particular threat for dividing cells, as: (i) it occurs frequently in early mitosis; (ii) it is not detected by the spindle assembly checkpoint (unlike other types of mis-attachments); (iii) it can lead to chromosome mis-segregation, and, hence, aneuploidy. A number of studies have recently started to unveil the cellular and molecular mechanisms involved in merotelic kinetochore formation and correction. Here, I review these studies and discuss the relevance of merotelic kinetochore orientation in cancer cell biology.
Cimini
Daniela
D
Virginia Tech, Department of Biological Sciences, 5036 Derring Hall, Blacksburg, VA 24061, USA. cimini@vt.edu
D025601:Adenomatous Polyposis Coli Protein / Q000502:physiology; D000782:Aneuploidy; D000818:Animals; D064127:Aurora Kinases; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology*; D033481:Chromosomes, Mammalian / Q000502:physiology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D018386:Kinetochores / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology; D009369:Neoplasms / Q000209:etiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D012097:Repressor Proteins; D008941:Spindle Apparatus / Q000502:physiology; D000077022:Survivin
D025601:Adenomatous Polyposis Coli Protein; C117749:Birc5 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; C513185:Incenp protein, mouse; D051034:Inhibitor of Apoptosis Proteins; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D012097:Repressor Proteins; D000077022:Survivin; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases