Abstract 3784: Regulation of chromatin condensation by mitotic checkpoint protein MAD2

Abstract

Abstract The process of cell division is stringently regulated by spindle and mitotic checkpoint components mainly MAD2, MAD1, CDC20, BUBR1, BUB3 and MAD3. These checkpoint proteins detect unattached or improperly attached kinetochore-microtubule binding sites and generate an anaphase-wait signal by inhibiting the anaphase-promoting complex (APC/C). Activation of checkpoint signaling arrests the cells at metaphase until the attachment errors are rectified and all the chromosomes are properly bi-oriented at the metaphase plate. Together with these checkpoint proteins, the expression of checkpoint-regulatory factors such as p31 (comet) and recently identified, WT1 can hypo- or hyper-activate the signaling pathway, respectively and regulate the timing of mitotic exit. Recently we found that WT1 can interact with MAD2 and regulate the mitotic checkpoint function. Furthermore our studies show that MAD2 and WT1 can also influence the chromatin condensation process required for mitotic progression. We analyzed the effect of MAD2 and WT1 perturbations on the epigenetic mark (phosphorylation of histone H3) associated with condensed chromatin state. Our results show that MAD2 regulates the recruitment of chromatin modifying enzyme Aurora kinase B during mitosis. We further show that MAD2 is an important factor required for synchronization of key events beyond the checkpoint signaling sites to ensure the fidelity of chromosome segregation. Citation Format: Jayasha Shandilya, Stefan GE Roberts. Regulation of chromatin condensation by mitotic checkpoint protein MAD2. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3784. doi:10.1158/1538-7445.AM2015-3784