Super hotspots and super coldspots in the repair of UV-induced DNA damage in the human genome.

Content Provider	Europe PMC
Author	Jiang, Yuchao Li, Wentao Lindsey-Boltz, Laura A. Yang, Yuchen Li, Yun Sancar, Aziz
Copyright Year	2021
Abstract	The formation of UV-induced DNA damage and its repair are influenced by many factors that modulate lesion formation and the accessibility of repair machinery. However, it remains unknown which genomic sites are prioritized for immediate repair after UV damage induction, and whether these prioritized sites overlap with hotspots of UV damage. We identified the super hotspots subject to the earliest repair for (6-4) pyrimidine–pyrimidone photoproduct by using the eXcision Repair-sequencing (XR-seq) method. We further identified super coldspots for (6-4) pyrimidine–pyrimidone photoproduct repair and super hotspots for cyclobutane pyrimidine dimer repair by analyzing available XR-seq time-course data. By integrating datasets of XR-seq, Damage-seq, adductSeq, and cyclobutane pyrimidine dimer-seq, we show that neither repair super hotspots nor repair super coldspots overlap hotspots of UV damage. Furthermore, we demonstrate that repair super hotspots are significantly enriched in frequently interacting regions and superenhancers. Finally, we report our discovery of an enrichment of cytosine in repair super hotspots and super coldspots. These findings suggest that local DNA features together with large-scale chromatin features contribute to the orders of magnitude variability in the rates of UV damage repair.
ISSN	00219258
Volume Number	296
PubMed Central reference number	PMC8081918
PubMed reference number	33771559
Journal	The Journal of Biological Chemistry [J. Biol. Chem]
e-ISSN	1083351X
DOI	10.1016/j.jbc.2021.100581
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2021-01-01
Access Restriction	Open
Rights License	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). © 2021 The Authors
Subject Keyword	nucleotide excision repair excision repair-sequencing cyclobutane pyrimidine dimer (6-4) pyrimidine–pyrimidone photoproduct (6-4)PPs, (6-4) pyrimidine–pyrimidone photoproducts CPD, cyclobutane pyrimidine dimer FIREs, frequently interacting regions GEO, Gene Expression Omnibus Hi-C, high-throughput chromosome conformation capture NGS, next-generation sequencing NHF1, normal human skin fibroblast 1 NTS, nontranscribed strand TADs, topologically associating domains TCR, transcription-coupled repair TFIIH, Transcription factor II H TS, transcribed strand XR-seq, eXcision Repair-sequencing
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Biochemistry