Journal Article

Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events

Kaya, Veysel Ogulcan, Lindsey-Boltz, Laura, Karagoz, Zeynep, Larsen, Peter A., Brown, Adam D., Sancar, Aziz, Adebali, Ogun, Akkose, Umit, Yoder, Anne D.

2021

Overview

Background Nucleotide excision repair is the primary DNA repair mechanism that removes bulky DNA adducts such as UV-induced pyrimidine dimers. Correspondingly, genome-wide mapping of nucleotide excision repair with eXcision Repair sequencing (XR-seq), provides comprehensive profiling of DNA damage repair. A number of XR-seq experiments at a variety of conditions for different damage types revealed heterogenous repair in the human genome. Although human repair profiles were extensively studied, how repair maps vary between primates is yet to be investigated. Here, we characterized the genome-wide UV-induced damage repair in gray mouse lemur, Microcebus murinus , in comparison to human. Results We derived fibroblast cell lines from mouse lemur, exposed them to UV irradiation, and analyzed the repair events genome-wide using the XR-seq protocol. Mouse lemur repair profiles were analyzed in comparison to the equivalent human fibroblast datasets. We found that overall UV sensitivity, repair efficiency, and transcription-coupled repair levels differ between the two primates. Despite this, comparative analysis of human and mouse lemur fibroblasts revealed that genome-wide repair profiles of the homologous regions are highly correlated, and this correlation is stronger for highly expressed genes. With the inclusion of an additional XR-seq sample derived from another human cell line in the analysis, we found that fibroblasts of the two primates repair UV-induced DNA lesions in a more similar pattern than two distinct human cell lines do. Conclusion Our results suggest that mouse lemurs and humans, and possibly primates in general, share a homologous repair mechanism as well as genomic variance distribution, albeit with their variable repair efficiency. This result also emphasizes the deep homologies of individual tissue types across the eukaryotic phylogeny.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: (6–4)PP / Adducts / Animal Genetics and Genomics / Animals / Asymmetry / Biomedical and Life Sciences / Cell lines / Comparative analysis / Comparative and evolutionary genomics / CPD / Damage / Deoxyribonucleic acid / Dimers / Divergent evolution / DNA / DNA adducts / DNA damage / DNA Damage - genetics / DNA fingerprinting / DNA repair / DNA Repair - genetics / DNA sequencing / Efficiency / Fibroblasts / Gene mapping / Genetic aspects / Genetic research / Genome, Human / Genomes / Genomics / Homology / Human beings / Humans / Irradiation / Life Sciences / Man / Microarrays / Microbial Genetics and Genomics / Microcebus murinus / Mouse Lemur / Nucleotide excision repair / Nucleotides / Phylogeny / Physiological aspects / Plant Genetics and Genomics / Primates / Primates - genetics / Proteomics / Pyrimidine Dimers / Repair / Research Article / RNA polymerase / Transcription / Transcription-coupled repair / Ultraviolet radiation / Ultraviolet Rays / UV damage / XR-seq