Kinetochores are the chromosomal sites for spindle interaction and play a vital role for chromosome segregation. Fission Saccharomyces cerevisiae kinetochore protein Mis12, is required for correct spindle morphogenesis, determining metaphase spindle length []. Thirty-five to sixty percent extension of metaphase spindle length takes place in Mis12 mutants []. It has been shown that Mis12 might genetically interact with Mal2p [].
This domain is found in Knl1, a sub-unit of the KMN network, present in Homo sapiens. The KMN network is the core of the outer kinetochore which is responsible for microtubule binding/stabilization and controls the spindle assembly checkpoint. This domain is the second of two RING finger, WD repeat, DEAD-like helicase (RWD) domains. The tandem RWD domains mediate kinetochore targeting of the microtubule-binding subunits by interacting with the Mis12 complex. The Mis12 complex is a KMN sub-complex that tethers directly onto the underlying chromatin layer [].
CENP-C is a vertebrate family that forms a core component of the centromeric chromatin. On depletion of CENP-C, proper formation of both centromeres and kinetochores is prevented. In kinetochores, the KMN (KNL1/Mis12/Ndc80) network regulates kinetochore microtubule binding []. The N-terminal of CENP-C is necessary for recruitment of some but not all components of the Mis12 complex to centromeres [, ].
This entry includes polyamine-modulated factor 1 (PMF1) from animals and Nnf1 from yeasts. PMF1 is part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis []. Nnf1 is an essential component of the MIND kinetochore complex required for accurate chromosome segregation [].
ZW10 interactor (also known as Zwint-1) is part of the MIS12 complex, which is required for kinetochore formation and spindle checkpoint activity []. It recruits ZW10 to unattached kinetochores at prometaphase []. It is essential for stable binding of a Mad1-Mad2 complex to unattached kinetochores []. It can be phosphoryltated by Aurora B (AurB) kinase [].
Chromobox protein homologue 3 (CBX3, also known as HP1 gamma) is a component of heterochromatin that binds histone H3 tails methylated at 'Lys-9' which leads to epigenetic repression []. By interacting with MIS12 complex, it is involved in the formation of a functional kinetochore []. It recruits NIPBL to sites of DNA damage at double-strand breaks []. It is a component of the E2F6.com-1 []and PER []complexes. The PER complex controls the circadian clock [].
The KMN network (for KNL1, MIS12 and NDC80 complexes) is a hub for signalling at the outer kinetochore []that acts as a receptor for both microtubules and checkpoint proteins []. Kinetochore scaffold 1, also known as Blinkin or KNL1, is a component of the KMN network. It is required to localize a subset of outer kinetochore proteins and is essential for chromosome segregation [, ].
Rod, the Rough deal protein (also known as Kinetochore-associated protein 1) displays a dynamic intracellular staining pattern, localising first to kinetochores in pro-metaphase, but moving to kinetochore microtubules at metaphase. Early in anaphase the protein is once again restricted to the kinetochores, where it persists until the end of telophase. This behaviour is in all respects similar to that described for ZW10 [], and indeed the two proteins function together, localisation of each depending upon the other []. These two proteins are found at the kinetochore in complex with a third, Zwilch, in both flies and humans. The C- terminus is the most conserved part of the protein. During pro-metaphase, the ZW10-Rod complex, dynein/dynactin, and Mad2 all accumulate on unattached kinetochores; microtubule capture leads to Mad2 depletion as it is carried off by dynein/dynactin; ZW10-Rod complex accumulation continues, replenishing kinetochore dynein. The continuing recruitment of the ZW10-Rod complex during metaphase may serve to maintain adequate dynein/dynactin complex on kinetochores for assisting chromatid movement during anaphase[]. The ZW10-Rod complex acts as a bridge whose association with Zwint-1 links Mad1 and Mad2, components that are directly responsible for generating the diffusible 'wait anaphase' signal, to a structural, inner kinetochore complex containing Mis12 and KNL-1AF15q14, the last of which has been proved to be essential for kinetochore assembly in Caenorhabditis elegans. Removal of ZW10 or Rod inactivates the mitotic checkpoint [].
