Transcription activity contributes to the firing of non-constitutive origins in African trypanosomes helping to maintain robustness in S-phase duration
| Autor: | Christiane B. de Araujo, Andréa Rodrigues Ávila, Marcelo S. Reis, Bruno B. Scholl, Priscila M. Hiraiwa, Gustavo R. Cayres-Silva, Paula A. Marin, Marcela O. Vitarelli, Maria Carolina Elias, Richard McCulloch, Marcelo Santos da Silva |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
DNA Replication
G2 Phase 0301 basic medicine Genome instability Trypanosoma brucei brucei lcsh:Medicine Double-strand DNA breaks Replication Origin Biology Trypanosoma brucei Genome Article Genomic Instability S Phase Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein Domains Transcription (biology) Parasite genetics Computer Simulation lcsh:Science Genetics Stochastic Processes Multidisciplinary DNA synthesis Cell Cycle lcsh:R DNA replication Robustness (evolution) RNA Origin firing biology.organism_classification Parasite biology 030104 developmental biology Microscopy Fluorescence chemistry lcsh:Q Monte Carlo Method 030217 neurology & neurosurgery DNA DNA Damage |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-19 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The co-synthesis of DNA and RNA potentially generates conflicts between replication and transcription, which can lead to genomic instability. In trypanosomatids, eukaryotic parasites that perform polycistronic transcription, this phenomenon and its consequences are still little studied. Here, we showed that the number of constitutive origins mapped in the Trypanosoma brucei genome is less than the minimum required to complete replication within S-phase duration. By the development of a mechanistic model of DNA replication considering replication-transcription conflicts and using immunofluorescence assays and DNA combing approaches, we demonstrated that the activation of non-constitutive (backup) origins are indispensable for replication to be completed within S-phase period. Together, our findings suggest that transcription activity during S phase generates R-loops, which contributes to the emergence of DNA lesions, leading to the firing of backup origins that help maintain robustness in S-phase duration. The usage of this increased pool of origins, contributing to the maintenance of DNA replication, seems to be of paramount importance for the survival of this parasite that affects million people around the world. |
| Databáze: | OpenAIRE |
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