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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Transcription activity contributes to the firing of non-constitutive origins in African trypanosomes helping to maintain robustness in S-phase duration

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Author(s):
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da Silva, Marcelo S. [1] ; Cayres-Silva, Gustavo R. [1] ; Vitarelli, Marcela O. [1] ; Marin, Paula A. [1] ; Hiraiwa, Priscila M. [2] ; Araujo, Christiane B. [1] ; Scholl, Bruno B. [1] ; Avila, Andrea R. [3] ; McCulloch, Richard [4] ; Reis, Marcelo S. [1] ; Elias, Maria Carolina [1]
Total Authors: 11
Affiliation:
[1] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Lab Especial Ciclo Celular, Sao Paulo - Brazil
[2] Fiocruz MS, Inst Carlos Chagas, Plataforma Citometria Fluxo, Curitiba, Parana - Brazil
[3] Fiocruz MS, Inst Carlos Chagas, Lab Regulacao Expressao Genica, Curitiba, Parana - Brazil
[4] Univ Glasgow, Wellcome Ctr Mol Parasitol, Inst Infect Immun & Inflammat, Glasgow, Lanark - Scotland
Total Affiliations: 4
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 9, DEC 6 2019.
Web of Science Citations: 0
Abstract

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. (AU)

FAPESP's process: 15/10580-0 - Characterization of intra-S checkpoint in Trypanosoma cells
Grantee:Maria Carolina Quartim Barbosa Elias Sabbaga
Support type: Regular Research Grants
FAPESP's process: 17/07693-2 - Functional dynamics of Orc1b protein during the life cycle of Trypanosoma
Grantee:Marcela de Oliveira Vitarelli
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/18719-2 - Structural analysis of the origin recognition complex (ORC) in Trypanosoma brucei using cryo-electron microscopy and single-particle analysis
Grantee:Marcelo Santos da Silva
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 16/17775-3 - Design and simulation of computational models of the DNA replication dynamics in kinetoplastids
Grantee:Gustavo Rodrigues Cayres Silva
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 14/24170-5 - DNA replication dynamics in Trypanosoma cruzi: licensing and replication rate characterization
Grantee:Marcelo Santos da Silva
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 16/50050-2 - How do common and diverged features of the replicative stress response shape the biology of TriTryp parasites?
Grantee:Maria Carolina Quartim Barbosa Elias Sabbaga
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 14/13375-5 - Replication origins in trypanosomes
Grantee:Christiane Bezerra de Araujo
Support type: Scholarships in Brazil - Post-Doctorate