Chromosome Structure and Function
Regulation of size, shape, and functions of chromosomes during mitosis
Chromosomes in interphase are relatively decondensed and support DNA replication and transcription during interphase. In contrast, mitotic chromosomes are more condensed and individualized to support chromosome segregation. Moreover, chromosomes in interphase stimulate distinct signals to assemble the nuclear envelope, but in mitosis, the nuclear envelope breaks down and chromosomes promote assembly of the spindle microtubules. We aim to understand molecular mechanisms behind these structural and functional changes of chromosomes at the cell cycle transitions between interphase and mitosis.
The nucleosome, where ~146 bp DNA wraps around core histone octamers, is the fundamental unit of chromatin. The linker histone interacts with the entry and exit points of nucleosomal DNAs. Using Xenopus egg extracts, we have developed a strategy to directly manipulate histone compositions & specific residues/modifications, and then monitor the functional, compositional and structural consequences.
How are chromosome shape and size mechanistically defined? How can nucleosomes and linker histones control long-range DNA compaction during mitosis? What is the mechanism that determines rigidity and flexibility of chromosomes?
We are addressing this question through combining biochemistry, imaging and cryo-EM.
What are the constituents of mitotic chromatin and how are they built?
Combining quantitative mass spectrometry and Xenopus egg extracts, we are in the unique position of being able to examine the direct role of specific histone modifications and mitotic regulators in chromatin composition and functions.