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Cell Div
2009 Jul 14;4:15. doi: 10.1186/1747-1028-4-15.
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Responding to chromosomal breakage during M-phase: insights from a cell-free system.
Smith E, Costanzo V.
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DNA double strand breaks (DSBs) activate ATM and ATR dependent checkpoints that prevent the onset of mitosis. However, how cells react to DSBs occurring when they are already in mitosis is poorly understood. The Xenopus egg extract has been utilized to study cell cycle progression and DNA damage checkpoints. Recently this system has been successfully used to uncover an ATM and ATR dependent checkpoint affecting centrosome driven spindle assembly. These studies have led to the identification of XCEP63 as major target of this pathway. XCEP63 is a coiled-coil rich protein localized at centrosome essential for proper spindle assembly. ATM and ATR directly phosphorylate XCEP63 on serine 560 inducing its delocalization from centrosome, which in turn delays spindle assembly. This pathway might contribute to regulate DNA repair or mitotic cell survival in the presence of chromosome breakage.
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Figure 1. Proposed model: ATM and ATR mediated XCEP63 phosphorylation promotes its removal from centrosome delaying spindle assembly. Depending on the number of DNA breaks this can lead to mitotic progression delay or mitotic cell death.
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