Incenp, short for Inner Centromere Protein, is crucial for correct chromosome segregation during mitosis. It is a key component of the chromosomal passenger complex (CPC), which has diverse functions in cell division. Incenp connects the kinase Aurora B to the inner centromere, allowing the kinase to access its kinetochore targets. Additionally, an ATM-Chk2-Incenp pathway has been identified, which activates the abscission checkpoint in response to chromatin bridges, preventing chromosome breakage or tetraploidization [1,2].

During cell division, inhibition of ATM or Chk2 kinases impairs CPC localization to the midbody center, accelerates midbody resolution, and leads to premature abscission and chromatin breakage in cytokinesis with trapped chromatin. In cultured human cells, ATM activates Chk2 at late midbodies, and Chk2 phosphorylates human Incenp-Ser91. This phosphorylation promotes Incenp binding to Mklp2 kinesin and CPC localization to the midbody center through Mklp2 association with Cep55 [1]. Expression of truncated Mklp2 that does not bind to Cep55 or non-phosphorylatable Incenp-Ser91A impairs CPC midbody localization and accelerates abscission, while phosphomimetic Incenp-Ser91D or a chimeric Incenp protein targeted to the midbody center rescues the abscission delay in Chk2-deficient or ATM-deficient cells [1].

In conclusion, Incenp is essential for proper chromosome segregation and regulation of cell division processes. The ATM-Chk2-Incenp pathway, as revealed through functional studies, plays a vital role in preventing chromatin breakage during cytokinesis. Understanding Incenp's functions can provide insights into the mechanisms underlying normal cell division and potentially shed light on diseases related to abnormal cell division, such as cancer.