Understanding bias in DNA repair

Terence R Strick, Nigel Savery

Research output: Contribution to journalComment/debate (Academic Journal)peer-review

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Abstract

DNA damage is a frequent and detrimental event faced by all living organisms. Decades of research have characterized the repair pathways that counteract this threat at genetic, biochemical, and structural levels. More recently, genome sequencing has revealed patterns of mutation demonstrating that DNA repair proteins fight damage more efficiently in some regions than others (1). Techniques that monitor DNA repair directly at a genome-wide scale promise greater insight into the mechanistic basis of these repair biases and provide a stringent testbed for models derived from biochemical data (2, 3). In PNAS, Adebali et al. (4) provide the first genome-wide picture of nucleotide excision repair (NER) in bacteria.

NER is a broad-specificity pathway present in both eukaryotes and prokaryotes. Substrates include the pyrimidine dimers induced by a potent environmental mutagen, UV light. There are at least two major subpathways of NER: Damage in untranscribed DNA is recognized and repaired by “global” NER, whereas faster, transcription-coupled NER processes target lesions in genes that are being expressed (5). The two pathways differ primarily at the damage recognition step. During global NER, lesions are detected by dedicated repair proteins. In transcription-coupled repair (TCR), the damage is first detected by RNA polymerase (RNAP), which stalls at a DNA lesion and triggers the assembly of repair complexes. Because only one of the two DNA strands is …
Original languageEnglish
Pages (from-to)2791-2793
Number of pages3
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number11
Early online date6 Mar 2017
DOIs
Publication statusPublished - 14 Mar 2017

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