Year: 2022
Type: article
Abstract: Exposure to ultraviolet (UV) light causes the formation of mutagenic cyclobutane pyrimidine dimers (CPDs) in cellular DNA. Previous studies have revealed that CPD formation in nucleosomes, the building blocks of chromatin, shows a striking ∼10 base pair (bp) periodic pattern. CPD formation is suppressed at positions where the DNA minor groove faces toward the histone octamer (minor-in) and elevated CPD formation at positions where the minor groove faces away from the histone octamer (minor-out). However, the molecular mechanism underlying this nucleosome photofootprint is unclear. Here, we analyzed ∼180 high-resolution nucleosome structures to characterize whether differences in DNA mobility or conformation are responsible for the CPD modulation in nucleosomes. Our results indicate that differences in DNA mobility cannot explain CPD modulation in nucleosome. Instead, we find that the sharp DNA bending around the histone octamer results in DNA conformations with structural parameters more susceptible to UV damage formation at minor-out positions and more resistant to CPD formation at minor-in positions. This analysis reveals the molecular mechanism responsible for periodic modulation of CPD formation and UV mutagenesis in nucleosomal DNA.
Institutions: Washington State University, Georgia State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,800
Awards: G5026347969, Direct chemical control of the hematopoietic master transcription factor PU.1, Folded state dynamics and hydration in transcriptional regulation, A cellular osmotic pressure sensor, G822426092, Regulation of DNA Excision Repair in Chromatin, Genome-wide analysis of the formation and mutagenesis of atypical UV photoproducts in skin cancer
OpenAlex ID: W4295778542