Centromeres are chromosome loci that are directing equal segregation of duplicated chromosomes during cell division. Lack of functional centromeres thus results in cells with too many or too few chromosomes. Chromosome misbalance in somatic cells is usually associated with cancers, while if happens in reproductive cells, result is offspring with genetic disorders (best know being Down syndrome). Centromeres are defined epigenetically by CENtromeric Protein A (CENP-A). This histone H3 variant assembles in a specialized nucleosome that serves as an anchor point for a complex protein machinery that forms on top of it during mitosis and assures that duplicated chromosomes attach to opposite poles of the dividing cell. I will talk how I used biophysical and biochemical approaches to uncover unique features of the specialized nucleosome at centromeres.
Relevant literature:
1. Falk SJ, Lee J, Sekulic N, Sennett MA, Lee TH, Black BE. CENP-C directs a structural transition of CENP-A nucleosomes mainly through sliding of DNA gyres. Nat Struct Mol Biol. 2016 Mar;23(3):204-8.
2. Falk JS*, Guo JY*, Sekulic N*, Smoak EM*, Mani T, Logsdon G, Gupta K, Jansen LT, Van Duyne GV, Vinogradov SA, Lampson MA, and Black BE. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere. Science. 2015 May 8;348(6235):699-703
* - Denotes equal contributions - co-authorship
3. Sekulic N, Bassett EA, Rogers DJ, Black BE. The structure of (CENP-A-H4)2 reveals physical features that mark centromeres. Nature. 2010 Sep 16;467(7313):347-51