Kose Cansu, Lindsey-Boltz Laura A, Sancar Aziz, Jiang Yuchao
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Department of Statistics, College of Arts and Sciences, Texas A&M University, College Station, TX 77843, USA.
bioRxiv. 2024 Mar 29:2023.10.12.562083. doi: 10.1101/2023.10.12.562083.
Bulky DNA adducts such as those induced by ultraviolet light are removed from the genomes of multicellular organisms by nucleotide excision repair, which occurs through two distinct mechanisms, global repair, requiring the DNA damage recognition-factor XPC (xeroderma pigmentosum complementation group C), and transcription-coupled repair (TCR), which does not. TCR is initiated when elongating RNA polymerase II encounters DNA damage, and thus analysis of genome-wide excision repair in XPC-mutants only repairing by TCR provides a unique opportunity to map transcription events missed by methods dependent on capturing RNA transcription products and thus limited by their stability and/or modifications (5'-capping or 3'-polyadenylation). Here, we have performed the eXcision Repair-sequencing (XR-seq) in the model organism to generate genome-wide repair maps from a wild-type strain with normal excision repair, a strain lacking TCR (), or one that only repairs by TCR (-). Analysis of the intersections between the XR-seq repair maps with RNA-mapping datasets (RNA-seq, long- and short-capped RNA-seq) reveal previously unrecognized sites of transcription and further enhance our understanding of the genome of this important model organism.
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