Functional significance of substrate masking against phosphorylation and methylation for chromosome inheritance

Maintenance of genetic and epigenetic information is critical for cell proliferation, whose alteration could lead to developmental defects, immunodeficiencies, and cancers. While protein phosphorylation is a versatile modification that can transmit short (≤ min) timescale signaling information, DNA methylation acts as a long-term epigenetic mark, which can be inherited to progenies over the developmental and evolutionary timescales. We will present our two new studies
related to “substrate masking” of protein phosphorylation and DNA methylation by microtubules and nucleosomes, the universal architectural components integral for chromosome inheritance in eukaryotes. First, how context-dependent phosphorylation of a key kinetochore substrate by the kinase Aurora B during mitosis is regulated through a microtubule-mediated substrate masking
mechanism to ensure that all chromosomes are attached to microtubules in the correct orientation for their equal segregation. Second, how hemimethylated DNA masked by nucleosomes is sensed and resolved by the ICF (immunodeficiency, centromere instability and facial anomalies) disease-related CDCA7-HELLS nucleosome remodeling complex to facilitate effective maintenance of DNA methylation in compact chromatin.