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Merotelic kinetochore attachment: causes and effects.

Gregan J, Polakova S, Zhang L, Tolić-Nørrelykke IM, Cimini D - Trends Cell Biol. (2011)

Bottom Line: Accurate chromosome segregation depends on the proper attachment of sister kinetochores to microtubules emanating from opposite spindle poles.Merotelic kinetochore orientation is an error in which a single kinetochore is attached to microtubules emanating from both spindle poles.Despite correction mechanisms, merotelically attached kinetochores can persist until anaphase, causing chromatids to lag on the mitotic spindle and hindering their timely segregation.

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Affiliation: Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 1, 1030 Vienna, Austria. juraj.gregan@univie.ac.at

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Types of kinetochore attachments during mitosis. Whereas only one of the two sister kinetochores is attached to spindle microtubules in monotelic attachment, sister kinetochores are attached to microtubules emanating from opposite spindle poles in amphitelic attachment. Monotelic kinetochore attachment is an intermediate state preceding proper amphitelic attachment. There are two types of erroneous kinetochore attachments: syntelic attachment, where both sister kinetochores interact with microtubules emanating from the same spindle pole, and merotelic attachment, where a single kinetochore is connected to both spindle poles. There are 15–30 microtubule attachment sites at vertebrate kinetochores, thereby providing considerable opportunity for generating merotelic attachments. Three types of merotelic attachments have been observed: i) balanced merotelic (similar number of kinetochore microtubules attached from both poles), ii) mero-amphitelic (more kinetochore microtubules emanating from the pole opposite to that of the sister kinetochore) and iii) mero-syntelic (more kinetochore microtubules emanating from the pole to which the sister kinetochore is attached) [36,95]. Chromosomes with monotelic or syntelic attachments are also referred to as mono-oriented, whereas those with amphitelic or merotelic attachments are referred to as bioriented. To segregate chromosomes properly, erroneous kinetochore attachments should be corrected and amphitelic attachments stabilized.
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fig0020: Types of kinetochore attachments during mitosis. Whereas only one of the two sister kinetochores is attached to spindle microtubules in monotelic attachment, sister kinetochores are attached to microtubules emanating from opposite spindle poles in amphitelic attachment. Monotelic kinetochore attachment is an intermediate state preceding proper amphitelic attachment. There are two types of erroneous kinetochore attachments: syntelic attachment, where both sister kinetochores interact with microtubules emanating from the same spindle pole, and merotelic attachment, where a single kinetochore is connected to both spindle poles. There are 15–30 microtubule attachment sites at vertebrate kinetochores, thereby providing considerable opportunity for generating merotelic attachments. Three types of merotelic attachments have been observed: i) balanced merotelic (similar number of kinetochore microtubules attached from both poles), ii) mero-amphitelic (more kinetochore microtubules emanating from the pole opposite to that of the sister kinetochore) and iii) mero-syntelic (more kinetochore microtubules emanating from the pole to which the sister kinetochore is attached) [36,95]. Chromosomes with monotelic or syntelic attachments are also referred to as mono-oriented, whereas those with amphitelic or merotelic attachments are referred to as bioriented. To segregate chromosomes properly, erroneous kinetochore attachments should be corrected and amphitelic attachments stabilized.

Mentions: Chromosome segregation occurs thanks to the interaction between a microtubule-based bipolar spindle and kinetochores, proteinaceous complexes assembled on the centromeric heterochromatin of each chromosome [78]. The individual kinetochores of most eukaryotic cells are associated with multiple microtubules. For high-fidelity chromosome segregation, kinetochores must capture spindle microtubules and connect the sister chromatids of each chromosome to opposite spindle poles before anaphase onset. During anaphase, pulling forces of the spindle separate sister chromatids from each other to opposite spindle poles [79–83]. Thus, the attachment of sister kinetochores to microtubules emanating from opposite spindle poles (amphitelic attachment, Figure I) is necessary for accurate chromosome segregation. Commonly, at early mitotic stages, only one of the two sister kinetochores is attached to spindle microtubules (monotelic attachment) (Figure I) [84]. This is because the interaction between kinetochores and spindle microtubules is stochastic [85–88], and sister kinetochores rarely attach to microtubules simultaneously. In addition, two types of erroneous kinetochore attachments can occur during spindle assembly: syntelic attachment, where both sister kinetochores interact with microtubules that emanate from the same spindle pole (Figure I), and merotelic attachment, where a single kinetochore is connected to both spindle poles (Figure I, Figure II). If not corrected, erroneous kinetochore attachments might result in the mis-segregation of chromosomes during anaphase, leading to aneuploid progeny [89,90]. Therefore, it is important that the attachment of kinetochores to spindle microtubules is monitored by the SAC, which ensures that anaphase is triggered only after all kinetochores are attached to spindle microtubules [39,62,91]. In addition, correction mechanisms eliminate erroneous kinetochore attachments and promote correct (amphitelic) attachments [41,92–94]. This prevents the loss of unattached chromosomes and mis-segregation of incorrectly attached chromosomes during anaphase.


Merotelic kinetochore attachment: causes and effects.

Gregan J, Polakova S, Zhang L, Tolić-Nørrelykke IM, Cimini D - Trends Cell Biol. (2011)

Types of kinetochore attachments during mitosis. Whereas only one of the two sister kinetochores is attached to spindle microtubules in monotelic attachment, sister kinetochores are attached to microtubules emanating from opposite spindle poles in amphitelic attachment. Monotelic kinetochore attachment is an intermediate state preceding proper amphitelic attachment. There are two types of erroneous kinetochore attachments: syntelic attachment, where both sister kinetochores interact with microtubules emanating from the same spindle pole, and merotelic attachment, where a single kinetochore is connected to both spindle poles. There are 15–30 microtubule attachment sites at vertebrate kinetochores, thereby providing considerable opportunity for generating merotelic attachments. Three types of merotelic attachments have been observed: i) balanced merotelic (similar number of kinetochore microtubules attached from both poles), ii) mero-amphitelic (more kinetochore microtubules emanating from the pole opposite to that of the sister kinetochore) and iii) mero-syntelic (more kinetochore microtubules emanating from the pole to which the sister kinetochore is attached) [36,95]. Chromosomes with monotelic or syntelic attachments are also referred to as mono-oriented, whereas those with amphitelic or merotelic attachments are referred to as bioriented. To segregate chromosomes properly, erroneous kinetochore attachments should be corrected and amphitelic attachments stabilized.
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fig0020: Types of kinetochore attachments during mitosis. Whereas only one of the two sister kinetochores is attached to spindle microtubules in monotelic attachment, sister kinetochores are attached to microtubules emanating from opposite spindle poles in amphitelic attachment. Monotelic kinetochore attachment is an intermediate state preceding proper amphitelic attachment. There are two types of erroneous kinetochore attachments: syntelic attachment, where both sister kinetochores interact with microtubules emanating from the same spindle pole, and merotelic attachment, where a single kinetochore is connected to both spindle poles. There are 15–30 microtubule attachment sites at vertebrate kinetochores, thereby providing considerable opportunity for generating merotelic attachments. Three types of merotelic attachments have been observed: i) balanced merotelic (similar number of kinetochore microtubules attached from both poles), ii) mero-amphitelic (more kinetochore microtubules emanating from the pole opposite to that of the sister kinetochore) and iii) mero-syntelic (more kinetochore microtubules emanating from the pole to which the sister kinetochore is attached) [36,95]. Chromosomes with monotelic or syntelic attachments are also referred to as mono-oriented, whereas those with amphitelic or merotelic attachments are referred to as bioriented. To segregate chromosomes properly, erroneous kinetochore attachments should be corrected and amphitelic attachments stabilized.
Mentions: Chromosome segregation occurs thanks to the interaction between a microtubule-based bipolar spindle and kinetochores, proteinaceous complexes assembled on the centromeric heterochromatin of each chromosome [78]. The individual kinetochores of most eukaryotic cells are associated with multiple microtubules. For high-fidelity chromosome segregation, kinetochores must capture spindle microtubules and connect the sister chromatids of each chromosome to opposite spindle poles before anaphase onset. During anaphase, pulling forces of the spindle separate sister chromatids from each other to opposite spindle poles [79–83]. Thus, the attachment of sister kinetochores to microtubules emanating from opposite spindle poles (amphitelic attachment, Figure I) is necessary for accurate chromosome segregation. Commonly, at early mitotic stages, only one of the two sister kinetochores is attached to spindle microtubules (monotelic attachment) (Figure I) [84]. This is because the interaction between kinetochores and spindle microtubules is stochastic [85–88], and sister kinetochores rarely attach to microtubules simultaneously. In addition, two types of erroneous kinetochore attachments can occur during spindle assembly: syntelic attachment, where both sister kinetochores interact with microtubules that emanate from the same spindle pole (Figure I), and merotelic attachment, where a single kinetochore is connected to both spindle poles (Figure I, Figure II). If not corrected, erroneous kinetochore attachments might result in the mis-segregation of chromosomes during anaphase, leading to aneuploid progeny [89,90]. Therefore, it is important that the attachment of kinetochores to spindle microtubules is monitored by the SAC, which ensures that anaphase is triggered only after all kinetochores are attached to spindle microtubules [39,62,91]. In addition, correction mechanisms eliminate erroneous kinetochore attachments and promote correct (amphitelic) attachments [41,92–94]. This prevents the loss of unattached chromosomes and mis-segregation of incorrectly attached chromosomes during anaphase.

Bottom Line: Accurate chromosome segregation depends on the proper attachment of sister kinetochores to microtubules emanating from opposite spindle poles.Merotelic kinetochore orientation is an error in which a single kinetochore is attached to microtubules emanating from both spindle poles.Despite correction mechanisms, merotelically attached kinetochores can persist until anaphase, causing chromatids to lag on the mitotic spindle and hindering their timely segregation.

View Article: PubMed Central - PubMed

Affiliation: Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 1, 1030 Vienna, Austria. juraj.gregan@univie.ac.at

Show MeSH
Related in: MedlinePlus