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

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number600
JournalBMC Genomics
Volume22
Issue number1
DOIs
StatePublished - Aug 6 2021

Bibliographical note

Funding Information:
The design of the repair assays is supported by the National Institutes of Health [GM118102, ES027255 to A.S.]. Cell line establishment was supported by the National Science Foundation [DEB-1354610 to A.Y.D]. Conceptualization and computational analysis were supported by European Molecular Biology Organization Installation Grant (to O.A.) A.Y.D is supported by the John Simon Guggenheim Foundation, and the Alexander von Humboldt Foundation. O.A. is supported by TUBITAK 2232 International Fellowship for Outstanding Researchers Program and Young Scientist Grant (BAGEP) awarded by Science Academy, Turkey.

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • (6–4)PP
  • CPD
  • Mouse Lemur
  • Nucleotide excision repair
  • Primate
  • UV damage
  • XR-seq
  • DNA Damage/genetics
  • Humans
  • DNA Repair/genetics
  • Primates/genetics
  • Animals
  • Ultraviolet Rays
  • Genome, Human
  • Pyrimidine Dimers

PubMed: MeSH publication types

  • Journal Article

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