Better check late than never: The chromosome segregation checkpoint (comment on DOI 10.1002/bies.201400140).

Abstract

Aneuploidy is the result of errors in chromosome segregation and is manifested in two out of three cancers. The spindle assembly checkpoint (SAC) has evolved to prevent aneuploidy by inhibiting onset of anaphase until all chromosomes are properly aligned and attached. When the SAC is satisfied and cells progress from anaphase to telophase, the sister chromatids are separated and decondensed, and the nuclear envelope is reformed (NER). While the SAC detects many types of erroneous attachments that can lead to chromosome missegration, including monopolar or syntelic attachments (attachment to one pole only), it does not detect merotelic attachments, (one sister chromatid attached to both poles), as the latter type of attachments produce similar tension across sister chromatids as correct (amphitelic) attachments. When merotelic attachments are not resolved prior to anaphase, chromatids will lag behind during anaphase, compromising their segregation to the correct spindle pole. Lagging chromosomes often result in micronuclei, a major mechanism of chromosomal instability in cancer cells [1]. However, various lines of evidence indicate that incomplete chromosome separation can delay transition to telophase, suggesting a surveillance mechanism beyond the SAC, operating late in anaphase. For example, recent work from Helder Maiato and co-workers identified a