regulation of centromere formation. The N-terminal tails of histones can be modified in several ways, including phosphorylation, acetylation, methylation and ubiquitination. Although certain histone modifications at centromeres seem to serve a purpose—for example, contributing to a higher order organization of chromatins in mouse centromeres—conventional and neocentromeres share very few modifications but arguably still maintain the same function of a centromere. Histone chaperones Replenishment of CENPA every cycle, which is important for reestablishing centromere identity, is carried out by HJURP (Holliday Junction Recognition Protein), or Scm3 in fungi and CAL1 in Drosophila. Tethering HJURP to a non-centromeric locus can give rise to a neocentromere, even after the disassociation of HJURP. There seems to be a co-evolutionary relationship between the Drosophila chaperone CAL1 and CENPA which accounts for species incompatibility—this is discussed more below. Cell cycle coordination with CENPA deposition Whereas deposition of CENPA happens during S phase for S. cerevisiae, two pathways of CENPA deposition in S. pombe determine when CENPA is deposited, namely S phase and G2. In Arabidopsis thaliana, experiments suggest that CENPA deposition via a replication-independent mechanism in G2. For humans, the time seems to be during early G1. This temporal regulation is important as it reveals the composition of centromeric chromatin during the time of kinetochore assembly in mitosis. Perhaps reimaging the formation of neocentromeres from the perspective of the cell-cycle might reveal more about what type of regulation is necessary for centromere formation. Evolution One may expect, since the centromere plays such a significant role in chromosome segregation and general inheritance, that the centromere would be highly conserved, in sequence or in epigenetic regulation. However, even though the CENPA histone variant is in fact conserved, there is a surprisingly large amount of diversity in the organization of centromeric chromatin, across different lineages. Another striking thing in centromere evolution is that while centromere function is conserved among all eukaryotes the underlying DNA is rapidly evolving, this phenomenon has been coined as the "centromere paradox". Yeast, Drosophila and mammals all have heterochromatin flanking their centromeres. Although the vertebrate chaperone HJURP and the yeast chaperone Scm3 have diverged, their N-terminal domains show striking conservation. On the other hand, frogs and chickens have domains in their chaperones that are not at all shared with that of yeast. Hence, further research into the mechanistic properties of these chaperones may potentially reveal how they help determine where and what type of centromere