On April 1, Johnathan Higgins, a Professor of Medicine at Harvard, gave a presentation at the Geisel School of Medicine on his work investigating regulation of mitosis by histone modification.
In cellular replication, DNA condenses into chromosomes so that genetic information can more easily segregate. The goal in mitosis is to have sister chromatids (those with replicated genetic information) aligned side-by-side so that each daughter cell receives the correct genetic information. Failure to correctly segregate chromosomes can contribute to cancer and various birth defects.
Histone proteins are a critical part of DNA packing and thus chromosome formation. The histone proteins themselves have globular domains and tails. Groups of eight histones form nucleosomes; DNA wraps around these and the nucleosomes form the greater chromosome structure (Figure 1).
The histone proteins themselves have two domains: a globular domain and a tail. The tails project away from the nucleosome and can become modified by other proteins. Modifications can change the charge of the tails, thus altering DNA-histone interactions and changing the properties of chromatin; other modifications create binding sites for other proteins; finally, they can prevent other histone-binding proteins from carrying out their functions.
One protein, Haspin, phosphorylates (modifies) the third histone during mitosis. The Haspin protein is highly evolutionarily conserved (yeast, plants, animals, and amoeboflagellates). In experiments that render Haspin nonfunctional, the cell has chromosome alignment problems. Therefore, Higgins concluded, the modification Haspin imposes on the H3 protein must be important to mitosis.
The Haspin phosphorylation releases other histone-binding proteins from one end (the N-terminus) of H3 during mitosis. Specifically, the modification displaces a transcription factor.
Aurora B is another one of the many proteins involved in mitosis. Aurora B corrects errors in attachments between chromosomes and spindle – the structural element that attaches to sister chromatids and pulls them apart into the two daughter cells. Higgins found that Haspin’s histone modification is required to get Aurora B into the right location.
Various questions about the mechanism behind Haspin’s function still exist. Scientists do not understand how or when Haspin is initially triggered early in mitosis. Haspin is la common protein with important regularly effects, but one that has only recently been discovered and studied.