Determination of the Role of Irc20 in Preventing CAG Repeat Fragility.
Takacsi-Nagy, Oliver.
2018
- CAG repeat sequences pose a formidable challenge to DNA replication, transcription and repair due to their propensity to form stable secondary structures. Accordingly, CAG repeat tracts, which are common throughout the human genome, have been deemed prone to chromosomal breakage (fragility) and changes in repeat copy number (instability). Given these characterizations, CAG repeats are causally ... read moreassociated with a host of neurodegenerative disorders. It is thus valuable to identify and investigate the specific mechanisms by which hallmark disease pathologies diseases arise molecularly. This study utilizes the model organism S. cerevisiae, which can be altered to harbor CAG repeat tracts in various genomic locations, to characterize the role of Irc20 in preventing CAG repeat fragility, and more generally DNA repair. Irc20, previously categorized as an E3 ubiquitin ligase with chromatin remodeling capacity, was observed to prevent fragility using a YAC (yeast artificial chromosome) assay system. Subsequent epistatic analysis using this assay system yielded a synergistic relationship with Rad5, and function in the same pathway as Uls1. Moreover, Irc20 was shown to be necessary for efficient repair by sister chromatid recombination. These results point strongly towards a role in the Rad5-mediated error-free branch of post replication repair (PRR).read less
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- q524k0984
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- tufts:sd.0000838
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