“When condensins are depleted, the resulting dispersed microtubule attachment sites mediate massive merotelic attachments.”
“Knowlton AL, Lan W, Stukenberg PT (2006) Aurora B is enriched at merotelic attachment sites, where it regulates MCAK.”
“The insert schematic shows the arrangement of a merotelic kinetochore with attached microtubules.”
“Thus, condensin dysfunction synergistically induces merotelic attachments and compromises the merotelic attachment correction mechanism, leading to chromosome breaks and nondisjunction.”
“The EM images (Fig. 5) collectively reinforce the correlation between stretching of centromeric chromatin, spreading of microtubule-binding modules of individual kinetochores and a net increase in uncorrected syntelic, merotelic, and double-merotelic attachments in condensin-depleted cells.”
“Most merotelic attachments in wild type affect only one sister kinetochore and are corrected prior to anaphase, any (few) remaining mis-attachments are resolved upon application of anaphase pulling forces”
“While it is plausible that the stretched kinetochores in condensin-depleted chromatin have disoriented microtubule-binding sites that facilitate merotelic attachments, why would such mis-attachments remain uncorrected in metaphase and anaphase?”
“Aurora B activity in correcting syntelic and merotelic attachments”
“The extreme stretching of most centromeres is likely accompanied by a deformed/disrupted kinetochore structure, which precludes identification of most merotelic kihetochores by EM in fig. 5C-E.”
“To the contrary, we have found that unresolved merotelic attachment, as opposed to continuing pairing of sister chromatids after anaphase onset, is the primary contributor to missegregation that is accompanied by DNA damage late in mitosis.”
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