Asset Details
Do you wish to reserve the book?
Nucleosome positions establish an extended mutation signature in melanoma
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Nucleosome positions establish an extended mutation signature in melanoma
Do you wish to request the book?
Nucleosome positions establish an extended mutation signature in melanoma
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Nucleosome positions establish an extended mutation signature in melanoma
2018
Overview
Ultraviolet (UV) light-induced mutations are unevenly distributed across skin cancer genomes, but the molecular mechanisms responsible for this heterogeneity are not fully understood. Here, we assessed how nucleosome structure impacts the positions of UV-induced mutations in human melanomas. Analysis of mutation positions from cutaneous melanomas within strongly positioned nucleosomes revealed a striking ~10 base pair (bp) oscillation in mutation density with peaks occurring at dinucleotides facing away from the histone octamer. Additionally, higher mutation density at the nucleosome dyad generated an overarching \"translational curvature\" across the 147 bp of DNA that constitutes the nucleosome core particle. This periodicity and curvature cannot be explained by sequence biases in nucleosomal DNA. Instead, our genome-wide map of UV-induced cyclobutane pyrimidine dimers (CPDs) indicates that CPD formation is elevated at outward facing dinucleotides, mirroring the oscillation of mutation density within nucleosome-bound DNA. Nucleotide excision repair (NER) activity, as measured by XR-seq, inversely correlated with the curvature of mutation density associated with the translational setting of the nucleosome. While the 10 bp periodicity of mutations is maintained across nucleosomes regardless of chromatin state, histone modifications, and transcription levels, overall mutation density and curvature across the core particle increased with lower transcription levels. Our observations suggest structural conformations of DNA promote CPD formation at specific sites within nucleosomes, and steric hindrance progressively limits lesion repair towards the nucleosome dyad. Both mechanisms create a unique extended mutation signature within strongly positioned nucleosomes across the human genome.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Cancer
/ Chromatin - radiation effects
/ Cyclobutane pyrimidine dimers
/ DNA
/ Female
/ Funding
/ Genome, Human - radiation effects
/ Genomes
/ Genomics
/ Histone Code - radiation effects
/ Humans
/ Male
/ Medicine and Health Sciences
/ Melanoma
/ Mutation
/ Neoplasms, Radiation-Induced - genetics
/ Nucleosomes - radiation effects
/ Prostatic Neoplasms - genetics
/ Pyrimidine Dimers - genetics
/ Research and Analysis Methods
/ Skin
/ Software
