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Bioinformatic analyses of genome wide nucleotide excision repair datasets in Saccharomyces cerevisiae [Abstract]

Bennett, Mark Richard, Evans, Katie Ellen, Teng, Yumin, Leadbitter, Matthew, Yu, Shirong, Waters, Raymond, Giles, Peter James and Reed, Simon Huw 2012. Bioinformatic analyses of genome wide nucleotide excision repair datasets in Saccharomyces cerevisiae [Abstract]. Mutagenesis 27 (1) , p. 121. 10.1093/mutage/ger068

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Abstract

DNA is not chemically inert but faces constant challenges to its stability. One of these is the fusion of adjacent pyrimidine bases by ultra violet (UV) radiation to create cyclobutane pyrimidine dimers (CPDs). Numerous methods of DNA repair have evolved within cells, of which nucleotide excision repair (NER) is responsible for the removal of CPDs and other bulky adducts. To investigate this and other repair pathways various techniques have been developed to detect DNA damage at low resolutions in whole genomes or high resolutions over small sections of a genome. We have developed a novel microarray based method for the genome wide high resolution analysis of DNA damage in yeast which combines the advantages of these, allowing detailed measurement of repair across entire genomes. A program has been written to predict the expected CPD formation based on sequence; this has shown that the genome wide damage detection method is accurate. Additionally, ChIPchip has been used to determine the binding positions of proteins involved in NER and analyse histone modifications after damage induction. Combining these datasets allows protein binding and acetylation levels to be correlated with repair rates. These datasets require bioinformatic tools to analyse and extract results. I have developed a suite of novel tools to process, normalise, display and interrogate these datasets including a new normalisation method which allows accurate comparisons to be made between different factors, revealing changes in acetylation profiles following UV and between different mutant strains, a peak detection method to distinguish protein binding peaks from a background of nonbound regions, revealing many novel binding sites for proteins such as Abf1 and Rad16, and graphical displays to determine patterns that occur at multiple positions throughout genomes, revealing patterns of varying repair rates at regions such as centromeres and telomeres.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Additional Information: Abstracts of the 34th Annual Meeting of the United Kingdom Environmental Mutagen Society, 29th June - 1st July 2011. Held jointly with the Association for Radiation Research at the University of Nottingham, UK
Publisher: Oxford University Press
ISSN: 0267-8357
Last Modified: 11 Mar 2020 15:06
URI: http://orca-mwe.cf.ac.uk/id/eprint/43397

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