Centromere Biology

This theme investigates the epigenetic mechanisms that define and preserve centromere function and identity across species despite rapid evolution and wide variability in centromeric DNA sequences. It addresses the role of the centromere-specific histone variant CENP-A (also known as CenH3), associated proteins of the constitutive centromere-associated network (CCAN), chromatin structure dynamics, and DNA methylation patterns in maintaining centromere stability and kinetochore assembly. Understanding these epigenetic contributions is fundamental to centromere biology since many functional centromeres form on non-repetitive DNA or neocentromeres, underscoring the minimal or non-essential role of specific DNA sequences in centromere identity.

This theme focuses on recent high-resolution structural biology studies of the constitutive centromere-associated network (CCAN) and its interaction with CENP-A nucleosomes in humans. It explores the molecular architecture of the key CCAN subunits, their arrangement, and how these structures govern kinetochore nucleation and centromere-chromatin specificity. Bridging the gap between epigenetic definition and molecular assembly, elucidating these structures is vital for understanding kinetochore function, centromere maintenance through the cell cycle, and the molecular basis of chromosome segregation fidelity.

This theme examines the genomic and evolutionary dynamics of centromere DNA sequences, particularly tandem repeats and satellite DNA, their homogenization via recombination and replication processes, and chromosomal rearrangements involving centromeres. It studies inter-species centromere type transitions and spatial genome architecture influencing centromere evolution. These insights illuminate the genetic and structural basis of centromere diversification, contributing to karyotype evolution, genome stability, and speciation.