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Updated: May 1, 2026

Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
Published on: September 13, 2022
ATM-mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint
Chunying Yang1, Jianwei Hao2, Dejuan Kong3
1Department of Radiation Oncology, Houston Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Oncology, Drug Discovery Division, Southern Research Institute, Birmingham, AL 35205, USA.
Abstract:
The spindle assembly checkpoint (SAC), which blocks anaphase onset until all chromosomes have bi-oriented, is one of the key self-monitoring systems of the eukaryotic cell cycle for genome stability. The mitotic arrest-deficient protein 1 (Mad1), a critical component of the SAC, is hyperphosphorylated in mitosis. However, the kinases responsible for Mad1 phosphorylation and its functional significance are not fully understood. Here we report that Mad1 is phosphorylated on Serine 214 by the Ataxia-Telangiectasia Mutated (ATM) kinase, a critical DNA damage response protein also activated in mitosis and required for the SAC. We demonstrate that Mad1 Serine 214 phosphorylation promotes the formation of homodimerization of Mad1 and its heterodimerization with Mad2. Further we show that Mad1 Serine 214 phosphorylation contribute to activation of the SAC and the maintenance of chromosomal stability. Together, these findings reveal an important role of ATM-mediated Mad1 Serine 214 phosphorylation in mitosis.
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