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If not repaired, DPCs can interfere with key biological processes such as transcription and replication and activate programmed cell death. A growing body of evidence implicates nucleotide excision repair (NER), homologous recombination, and other mechanisms in the removal of DPCs. However, the effects of genomic context on DPC formation and removal have not been comprehensively addressed. Using a combination of next-generation sequencing and DPC enrichment via protein precipitation, we show that DPCs induced following exposure to formaldehyde are non-randomly distributed across the human genome, based on chromatin state. The data further show that the efficiency of DPC removal correlates with transcription at loci transcribed by RNA polymerase II. Data presented herein indicate that efficient removal of chromosomal DPCs requires both the Cockayne syndrome group B gene as well as \u201cdownstream\u201d\u00a0TC-NER factor xeroderma pigmentosum group A gene. In contrast, loci transcribed by RNA polymerase I showed no evidence of transcription-coupled DPC removal. Taken together, our results indicate that complex interactions between chromatin organization, transcriptional activity, and numerous DNA repair pathways dictate genomic patterns of DPC formation and removal.<\/jats:p>","DOI":"10.1093\/nar\/gkaf720","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T11:16:50Z","timestamp":1753960610000},"source":"Crossref","is-referenced-by-count":6,"title":["Genome-wide mapping of formaldehyde-induced DNA\u2013protein crosslinks reveals unique patterns of formation and transcription-coupled removal in mammalian cells"],"prefix":"10.1093","volume":"53","author":[{"given":"Duha","family":"Alshareef","sequence":"first","affiliation":[{"name":"University of Minnesota Department of Pharmacology, , Minneapolis , MN\u00a0 55455 ,","place":["United States"]},{"name":"University of Tabuk Department of Pharmacology, , Tabuk , Tabuk\u00a071491,\u00a0","place":["Saudi 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