page_title: Kinetochore
section_title: Verification of kinetochore–MT anchoring
hierarchical_section_title: Kinetochore / Function / Verification of kinetochore–MT anchoring
caption_attribution_description: English: Scheme of the different configurations of chromosome attachment to the mitotic spindle. More information in Maiato et al. 2004 Journal of Cell Science 117, 5461-5477 Español: Esquema de las diferentes configuraciones de anclaje de los cromosomas al huso mitótico. Más información en Maiato et al. 2004 Journal of Cell Science 117, 5461-5477
context_page_description: A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. Its proteins also help to hold the sister chromatids together and play a role in chromosome editing. Details of the specific areas of origin are unknown.
  Monocentric organisms, including vertebrates, fungi, and most plants, have a single centromeric region on each chromosome which assembles a single, localized kinetochore. Holocentric organisms, such as nematodes and some plants, assemble a kinetochore along the entire length of a chromosome.
  Kinetochores start, control, and supervise the striking movements of chromosomes during cell division. During mitosis, which occurs after chromosomes are duplicated in S phase, two sister chromatids are held together by a centromere. Each chromatid has its own kinetochore, which face in opposite directions and attach to opposite poles of the mitotic spindle apparatus.
context_section_description: During S-Phase, the cell duplicates all the genetic information stored in the chromosomes, in the process termed DNA replication. At the end of this process, each chromosome includes two sister chromatids, which are two complete and identical DNA molecules. Both chromatids remain associated by cohesin complexes until anaphase, when chromosome segregation occurs. If chromosome segregation happens correctly, each daughter cell receives a complete set of chromatids, and for this to happen each sister chromatid has to anchor (through the corresponding kinetochore) to MTs generated in opposed poles of the mitotic spindle. This configuration is termed amphitelic or bi-orientation.
  However, during the anchoring process some incorrect configurations may also appear:
  monotelic: only one of the chromatids is anchored to MTs, the second kinetochore is not anchored; in this situation, there is no centromeric tension, and the spindle checkpoint is activated, delaying entry in anaphase and allowing time for the cell to correct the error. If it is not corrected, the unanchored chromatid might randomly end in any of the two daughter cells, generating aneuploidy: one daughter cell would have chromosomes in excess and the other would lack some chromosomes.
  syntelic: both chromatids are anchored to MTs emanating from the same pole; this situation does not generate centromeric tension either, and the spindle checkpoint will be activated. If it is not corrected, both chromatids will end in the same daughter cell, generating aneuploidy.
  merotelic: at least one chromatid is anchored simultaneously to MTs emanating from both poles. This situation generates centromeric tension, and for this reason the spindle checkpoint is not activated. If it is not corrected, the chromatid bound to both poles will remain as a lagging chromosome at anaphase, and finally will be broken in two fragments, distributed between the daughter cells, generating aneuploidy.
  Both the monotelic and the syntelic configurations fail to generate centromeric tension and are detected by the spindle checkpoint. In contrast, the merotelic configuration is not detected by this control mechanism. However, most of these errors are detected and corrected before the cell enters in anaphase. A key factor in the correction of these anchoring errors is the chromosomal passenger complex, which includes the kinase protein Aurora B, its target and activating subunit INCENP and two other subunits, Survivin and  Borealin/Dasra B (reviewed by Adams and collaborators in 2001). Cells in which the function of this complex has been abolished by dominant negative mutants, RNAi, antibody microinjection or using selective drugs, accumulate errors in chromosome anchoring. Many studies have shown that Aurora B is required to destabilize incorrect anchoring kinetochore-MT, favoring the generation of amphitelic connections. Aurora B homolog in yeast (Ipl1p) phosphorilates some kinetochore proteins, such as the constitutive protein Ndc10p and members of the Ndc80 and Dam1-DASH-DDD complexes. Phosphorylation of Ndc80 complex components produces destabilization of kMTs anchoring. It has been proposed that Aurora B localization is important for its function: as it is located in the inner region of the kinetochore (in the centromeric heterochromatin), when the centromeric tension is established sister kinetochores separate, and Aurora B cannot reach its substrates, so that kMTs are stabilized. Aurora B is frequently overexpressed in several cancer types, and it is currently a target for the development of anticancer drugs.
caption: Scheme showing different anchoring configurations between chromosomes and the mitotic spindle.[51]
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