Unknown,Transcriptomics,Genomics,Proteomics

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CPD-seq mapping of UV damage formation and repair in yeast


ABSTRACT: UV-induced DNA lesions are an important contributor to mutagenesis and cancer, but it is not fully understood how the chromosomal landscape influences UV lesion formation and repair. We have used a novel high-throughput sequencing method to precisely map UV-induced cyclobutane pyrimidine dimers (CPDs) at nucleotide resolution throughout the yeast genome. Analysis of CPD formation reveals that nucleosomal DNA having an inward rotational setting is protected from CPD lesions. In strongly positioned nucleosomes, this nucleosome 'photofootprint' overrides intrinsic dipyrimidine sequence preferences for CPD formation. CPD formation is also inhibited by DNA-bound transcription factors, in effect protecting important DNA elements from UV damage. Analysis of CPD repair revealed a clear signature of efficient transcription-coupled nucleotide excision repair. Repair was less efficient at translational positions near a nucleosome dyad and at heterochromatic regions in the yeast genome. These findings define the roles of nucleosomes and transcription factors in UV damage formation and repair. UV mapping data was analyzed for yeast cells irradiated with 125J/m2 and allowed to repair for 0hr (2 samples), 20 minutes, 1 hour, or 2 hours. Data is also included for naked DNA irradiated with UV 60 or 90 J/m2

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: John Wyrick 

PROVIDER: E-GEOD-79977 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Chromosomal landscape of UV damage formation and repair at single-nucleotide resolution.

Mao Peng P   Smerdon Michael J MJ   Roberts Steven A SA   Wyrick John J JJ  

Proceedings of the National Academy of Sciences of the United States of America 20160725 32


UV-induced DNA lesions are important contributors to mutagenesis and cancer, but it is not fully understood how the chromosomal landscape influences UV lesion formation and repair. Genome-wide profiling of repair activity in UV irradiated cells has revealed significant variations in repair kinetics across the genome, not only among large chromatin domains, but also at individual transcription factor binding sites. Here we report that there is also a striking but predictable variation in initial  ...[more]

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