| Full text | |
| Author(s): Show less - |
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 Opportunities: | 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 Opportunities: | 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 Opportunities: | 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 Opportunities: | 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 Opportunities: | Scholarships in Brazil - Post-Doctoral |
| 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 Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling |
| Grantee: | Hugo Aguirre Armelin |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 14/13375-5 - Replication origins in trypanosomes |
| Grantee: | Christiane Bezerra de Araujo |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |