Centromeres License the Mitotic Condensation of Yeast Chromosome Arms

Abstract

SummaryDuring mitosis, chromatin condensation shapes chromosomes as separate, rigid, and compact sister chromatids to facilitate their segregation. Here, we show that, unlike wild-type yeast chromosomes, non-chromosomal DNA circles and chromosomes lacking a centromere fail to condense during mitosis. The centromere promotes chromosome condensation strictly in cis through recruiting the kinases Aurora B and Bub1, which trigger the autonomous condensation of the entire chromosome. Shugoshin and the deacetylase Hst2 facilitated spreading the condensation signal to the chromosome arms. Targeting Aurora B to DNA circles or centromere-ablated chromosomes or releasing Shugoshin from PP2A-dependent inhibition bypassed the centromere requirement for condensation and enhanced the mitotic stability of DNA circles. Our data indicate that yeast cells license the chromosome-autonomous condensation of their chromatin in a centromere-dependent manner, excluding from this process non-centromeric DNA and thereby inhibiting their propagation.

Limits of chromosome compaction by loop-extruding motors

“…Surprisingly, one-sided loop extrusion can achieve only up to 10-fold compaction, even with LEF turnover. While this may be sufficient for yeast chromosomes [32], it cannot be the mechanism underlying ∼ 1000-fold mammalian chromosome compaction. We model LEFs as two-headed complexes with either one or two active heads ( Fig.…”

“…Moreover, these gaps cannot be reliably eliminated if the "safety belt" that anchors each one-sided LEF [31,39] instead freely diffuses along DNA because loop growth would be inhibited by configurational entropy [44]. 10-fold linear compaction may be sufficient for yeast chromosomes [32], but it is inconsistent with in vivo observations of > 100-fold linear compaction of mammalian chromosomes [4,5].…”

14-3-3 protein Bmh1 triggers short-range compaction of mitotic chromosomes by recruiting sirtuin deacetylase Hst2

“…H3 peptides phosphorylated at Ser-10 efficiently recovered Hst2 from yeast whole-cell extracts, demonstrating the significance of H3 S10 phosphorylation in recruiting Hst2 to mitotic chromatin (17). However, recombinant Hst2 purified from E. coli did not interact with H3 S10D peptides (a mutation that efficiently mimics H3 S10ph in vivo (17,19,22)) ( Supplementary Fig. S1), indicating that additional factors or PTMs on Hst2 are needed to mediate the interaction with H3 S10ph.…”

“…Chromosome condensation in mitosis is licensed by kinetochores via the recruitment of shugoshin and Hst2 (19). Phosphorylation of H3 S10 by Aurora kinase B is a central event in this process that mediates deacetylation of H4 K16ac by Hst2 (17,22).…”

“…Mechanistically, compaction by internucleosomal interactions is initiated by activation of Aurora kinase B at kinetochores. The signal subsequently propagates along chromosome arms in a shugoshin-dependent process, thereby coupling the ability of chromatin to condense to the presence of a centromere (19). This licensing of condensation by centromeres is a potential mechanism by which yeasts discriminate non-chromosomal DNA from chromosomes, protecting its progeny from infectious genetic material (19).…”