New Roles of Chk1 in Spindle Formation and Genome Integrity

During mitosis sister chromatids are accurately segregated into two daughter cells through a microtubule-based structure known as the mitotic spindle. Errors in mitotic spindle formation have been associated with human diseases and tumorigenesis. Chk1 has well established roles in DNA damage response and replication checkpoints. Recently, new roles have emerged in the onset of mitosis, chromosome segregation and cytokinesis. In this review, we recapitulate the known roles of Chk1 in cell division and highlight new roles of Chk1 in mitotic spindle assembly and its contribution to genome stability. Specifically, it was recently reported that, during the first stages of mitosis, ATRIP and its interacting partners, ATR and TopBP1, are recruited to centrosomes, where they activate Chk1. Then, Chk1 phosphorylates β-tubulin at Threonine 285 (T285), promoting microtubule nucleation and mitotic spindle formation. β-tubulin phosphorylation by Chk1 is required for proper mitotic progression, cytokinesis with equal-sized daughter cells and cell proliferation. This novel ATR-Chk1 signaling pathway reinforces the crosstalk between the cell cycle regulation and DNA damage response.