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Rita Cha group project:

Characterization of yeast fragile sites, Replication Slow Zones (RSZ)

As mentioned above, an essential feature of meiosis in many organisms is meiotic recombination that is initiated by the catalysis of hundreds of DSBs in the genome. In contrast, chromosome breaks do not normally arise during vegetative growth. However, unintended DSBs occasionally arise during normal proliferation as a result of either DNA damage and/or errors in normal DNA/chromosomal processes. These DSBs have been linked to genome instability and cell death. Notably, the breaks do not arise randomly throughout the genome but tend to cluster at specific loci referred to as fragile sites. Examples of fragile sites include the bacterial ter, the budding yeast replication slow zones (RSZs), and the mammalian common- and rare- fragile sites.

RSZs are genetic determinants that are about 10kb in size and are found in alternation with active replication origins along the entire length of a chromosome excluding the centromere region (Figure 3). The name RSZ stems from the observation that the rate of progression becomes notably slow as the forks enter these loci when compared to non-RSZs in the same chromosome. It was originally identified as loci prone to chromosome breakage following inactivation of Mec1. The name RSZ stems from the observation that the rate of progression becomes notably slow as the forks enter these loci when compared to non-RSZs in the same chromosome. In WT cells, forks continue to progress through RSZs, albeit more slowly, eventually completing the duplication of RSZs. In mec1 cells, replication forks arrive at RSZs but stall permanently until chromosomes break at these loci.

Figure 3

Figure 3

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Notable features on chromosome III of S. cerevisiae. Inactivation of Mec1 leads to cell death accompanied by chromosome breakage within yeast fragile sites referred to as RSZs (Replication Slow Zones; grey boxes). Other notable features of the chromosome include: active replication origins (open circles), centromere (fiilled oval), and replication termination sites (T). Phosphorylation of the axial element protein Hop1 by Mec1/Tel1 ensures meiotic interhomolog recombination.

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