Eukaryotic centromeres are maintained at specific chromosomal sites over many generations. In the budding yeast Saccharomyces cerevisiae, centromeres are genetic elements defined by a DNA sequence that is both necessary and sufficient for function; whereas, in most other eukaryotes, centromeres are maintained by poorly characterized epigenetic mechanisms in which DNA has a less definitive role. Here we use the pathogenic yeast Candida albicans as a model organism to study the DNA replication properties of centromeric DNA. By determining the genome-wide replication timing program of the C. albicans genome, we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome. Importantly, epigenetic formation of new ectopic centromeres (neocentromeres) was accompanied by shifts in replication timing, such that a neocentromere became the first to replicate and became associated with origin recognition complex (ORC) components. Furthermore, changing the level of the centromere-specific histone H3 isoform led to a concomitant change in levels of ORC association with centromere regions, further supporting the idea that centromere proteins determine origin activity. Finally, analysis of centromere-associated DNA revealed a replication-dependent sequence pattern characteristic of constitutively active replication origins. This strand-biased pattern is conserved, together with centromere position, among related strains and species, in a manner independent of primary DNA sequence. Thus, inheritance of centromere position is correlated with a constitutively active origin of replication that fires at a distinct early time. We suggest a model in which the distinct timing of DNA replication serves as an epigenetic mechanism for the inheritance of centromere position.
Eukaryotic centromeres are maintained at specific chromosomal sites over many generations . In the budding yeast Saccharomyces cerevisiae , centromeres are genetic elements defined by a DNA sequence that is both necessary and sufficient for function ; whereas , in most other eukaryotes , centromeres are maintained by poorly characterized epigenetic mechanisms in which DNA has a less definitive role . Here we use the pathogenic yeast Candida albicans as a model organism to study the DNA replication properties of centromeric DNA . By determining the genome - wide replication timing program of the C. albicans genome , we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome . Importantly , epigenetic formation of new ectopic centromeres ( neocentromeres ) was accompanied by shifts in replication timing , such that a neocentromere became the first to replicate and became associated with origin recognition complex ( ORC ) components . Furthermore , changing the level of the centromere - specific histone H3 isoform led to a concomitant change in levels of ORC association with centromere regions , further supporting the idea that centromere proteins determine origin activity . Finally , analysis of centromere - associated DNA revealed a replication - dependent sequence pattern characteristic of constitutively active replication origins . This strand - biased pattern is conserved , together with centromere position , among related strains and species , in a manner independent of primary DNA sequence . Thus , inheritance of centromere position is correlated with a constitutively active origin of replication that fires at a distinct early time . We suggest a model in which the distinct timing of DNA replication serves as an epigenetic mechanism for the inheritance of centromere position .
Do origins of replication close to yeast centromeres fire early or late?
Do origins of replication close to yeast centromeres fire early or late ?
Early
Early