You Heng Chuah, Emmy Xue Yun Tay, Oleg V Grinchuk, Jeehyun Yoon, Jia Feng, Srinivasaraghavan Kannan, Matius Robert, Rekha Jakhar, Yajing Liang, Bernice Woon Li Lee, Loo Chien Wang, Yan Ting Lim, Tianyun Zhao, Radoslaw M Sobota, Guang Lu, Boon Chuan Low, Karen Carmelina Crasta, Chandra Shekhar Verma, Zhewang Lin, Derrick Sek Tong Ong
MAD2 is a spindle assembly checkpoint protein that participates in the formation of mitotic checkpoint complex, which blocks mitotic progression. RNF8, an established DNA damage response protein, has been implicated in mitotic checkpoint regulation but its exact role remains poorly understood. Here, RNF8 proximity proteomics uncovered a role of RNF8-MAD2 in generating the mitotic checkpoint signal. Specifically, RNF8 competes with a small pool of p31comet for binding to the closed conformer of MAD2 via its RING domain, while CAMK2D serves as a molecular scaffold to concentrate the RNF8-MAD2 complex via transient/weak interactions between its p-Thr287 and RNF8's FHA domain...
July 19, 2023: Cell Death and Differentiation