التفاصيل البيبلوغرافية
| العنوان: |
An ATM–Chk2–INCENP pathway activates the abscission checkpoint. |
| المؤلفون: |
Petsalaki, Eleni1, Zachos, George1 gzachos@uoc.gr |
| المصدر: |
Journal of Cell Biology. Feb2021, Vol. 220 Issue 2, Following p1-23. 29p. |
| مصطلحات موضوعية: |
*CHIMERIC proteins, *CHROMATIN, *CYTOKINESIS, *CELL division, *AUTOMATED teller machines |
| مستخلص: |
During cell division, in response to chromatin bridges, the chromosomal passenger complex (CPC) delays abscission to prevent chromosome breakage or tetraploidization. Here, we show that inhibition of ATM or Chk2 kinases impairs CPC localization to the midbody center, accelerates midbody resolution in normally segregating cells, and correlates with premature abscission and chromatin breakage in cytokinesis with trapped chromatin. In cultured human cells, ATM activates Chk2 at late midbodies. In turn, Chk2 phosphorylates human INCENP-Ser91 to promote INCENP binding to Mklp2 kinesin and CPC localization to the midbody center through Mklp2 association with Cep55. Expression of truncated Mklp2 that does not bind to Cep55 or nonphosphorylatable INCENP-Ser91A impairs CPC midbody localization and accelerates abscission. In contrast, expression of phosphomimetic INCENP-Ser91D or a chimeric INCENP protein that is targeted to the midbody center rescues the abscission delay in Chk2-deficient or ATM-deficient cells. Furthermore, the Mre11–Rad50–Nbs1 complex is required for ATM activation at the midbody in cytokinesis with chromatin bridges. These results identify an ATM–Chk2–INCENP pathway that imposes the abscission checkpoint by regulating CPC midbody localization. [ABSTRACT FROM AUTHOR] |
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