Characterization of intra-S checkpoint in Trypanosoma cells

• Grant number: 15/10580-0
• Support type: Regular Research Grants
• Duration: November 01, 2015 - April 30, 2018
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal researcher: Maria Carolina Quartim Barbosa Elias Sabbaga
• Grantee: Maria Carolina Quartim Barbosa Elias Sabbaga
• Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Assoc. researchers: Carlos Renato Machado

Abstract

Cell cycle is a high controlled process and ensures that each cell receives the same genetic material from the mother cell. Therefore, cell cycle perturbations can delay or arrest cell cycle progression. The biochemical pathway that triggers this delay/arrest is named checkpoint. In this sense, checkpoints can be defined as G1/S checkpoint, intra-S checkpoint and G2/M checkpoint. Here we intend to investigate the presence of intra-S checkpoint in Trypanosoma when double single stranded breaks occur. Moreover, we intend to evaluate if this checkpoint acts (i) blocking DNA replication fork elongation and / or (ii) blocking the firing of new replication origins. Once confirmed a response to block DNA replication in the presence of damaged DNA, we intend to evaluate the role of ATM and ATR in this process. T. cruzi and T. brucei cells will be analyzed. Since these cells are early divergent eukaryotes this project aims to characterize intra-S checkpoint in these parasites and eventually describe new strategies to deal with damaged DNA. Moreover, T. brucei, but not T. cruzi, uses a double stranded break, generated during DNA replication, to induce the recombination process essential for antigenic variation and consequently for the success of infection. Therefore, understand how T. brucei deals with DNA damage may contribute to our knowledge concerning the process of T. brucei infection. It is important to say that if we observe lacking of intra-S checkpoint (which would be a very interesting data) we intend to verify the role of ATM and ATR in the G1/S or G2/M checkpoint in the presence of damaged DNA. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, MARCELO S.; PAVANI, RAPHAEL S.; DAMASCENO, JEZIEL D.; MARQUES, CATARINA A.; MCCULLOCH, RICHARD; ORSINI TOSI, LUIZ RICARDO; ELIAS, MARIA CAROLINA. Nuclear DNA Replication in Trypanosomatids: There Are No Easy Methods for Solving Difficult Problems. Trends in Parasitology, v. 33, n. 11, p. 858-874, NOV 2017. (16/50050-2, 14/24170-5, 15/10580-0, 13/07467-1)

DA SILVA, MARCELO SANTOS; MARIN MUNOZ, PAULA ANDREA; ARMELIN, HUGO AGUIRRE; ELIAS, MARIA CAROLINA. Differences in the Detection of BrdU/EdU Incorporation Assays Alter the Calculation for G1, S, and G2 Phases of the Cell Cycle in Trypanosomatids. Journal of Eukaryotic Microbiology, v. 64, n. 6, p. 756-770, NOV-DEC 2017. (14/24170-5, 15/10580-0, 13/07467-1)

DA SILVA, MARCELO SANTOS; SEGATTO, MARCELA; PAVANI, RAPHAEL SOUZA; GUTIERREZ-RODRIGUES, FERNANDA; BISPO, VANDERSON DA SILVA; GENNARI DE MEDEIROS, MARISA HELENA; CALADO, RODRIGO TOCANTINS; ELIAS, MARIA CAROLINA; NOGUEIRA CANO, MARIA ISABEL. Consequences of acute oxidative stress in Leishmania amazonensis: From telomere shortening to the selection of the fittest parasites. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1864, n. 1, p. 138-150, JAN 2017. (14/02978-0, 15/10580-0, 14/24170-5, 13/07467-1, 13/07937-8)

CRISPIM, MARCELL; DAMASCENO, FLAVIA SILVA; HERNANDEZ, AGUSTINO; BARISON, MARIA JULIA; SAUTER, ISMAEL PRETTO; PAVANI, RAPHAEL SOUZA; MOURA, ALEXANDRE SANTOS; FURUSHO PRAL, ELIZABETH MIEKO; CORTEZ, MAURO; ELIAS, MARIA CAROLINA; et al. The glutamine synthetase of Trypanosoma cruzi is required for its resistance to ammonium accumulation and evasion of the parasitophorous vacuole during host-cell infection. PLoS Neglected Tropical Diseases, v. 12, n. 1, JAN 2018. (16/50050-2, 16/06034-2, 14/10443-0, 15/10580-0, 13/07467-1)

PAVANI, RAPHAEL SOUZA; DA SILVA, MARCELO SANTOS; HENRIQUE FERNANDES, CARLOS ALEXANDRE; MORINI, FLAVIA SOUZA; ARAUJO, CHRISTIANE BEZERRA; DE MATTOS FONTES, MARCOS ROBERTO; SANT'ANNA, OSVALDO AUGUSTO; MACHADO, CARLOS RENATO; CANO, MARIA ISABEL; FRAGOSO, STENIO PERDIGAO; et al. Replication Protein A Presents Canonical Functions and Is Also Involved in the Differentiation Capacity of Trypanosoma cruzi. PLoS Neglected Tropical Diseases, v. 10, n. 12, DEC 2016. (14/13375-5, 14/24170-5, 13/17864-8, 14/02978-0, 13/07467-1, 15/10580-0)

MARIN, PAULA ANDREA; DA SILVA, MARCELO SANTOS; PAVANI, RAPHAEL SOUZA; MACHADO, CARLOS RENATO; ELIAS, MARIA CAROLINA. Recruitment kinetics of the homologous recombination pathway in procyclic forms of Trypanosoma brucei after ionizing radiation treatment. SCIENTIFIC REPORTS, v. 8, MAR 29 2018. (16/50050-2, 14/24170-5, 15/10580-0, 13/07467-1)

DA SILVA, MARCELO S.; CAYRES-SILVA, GUSTAVO R.; VITARELLI, MARCELA O.; MARIN, PAULA A.; HIRAIWA, PRISCILA M.; ARAUJO, CHRISTIANE B.; SCHOLL, BRUNO B.; AVILA, ANDREA R.; MCCULLOCH, RICHARD; REIS, MARCELO S.; et al. Transcription activity contributes to the firing of non-constitutive origins in African trypanosomes helping to maintain robustness in S-phase duration. SCIENTIFIC REPORTS, v. 9, DEC 6 2019. (15/10580-0, 17/07693-2, 17/18719-2, 16/17775-3, 14/24170-5, 16/50050-2, 13/07467-1, 14/13375-5)

MARIN, PAULA ANDREA; OBONAGA, RICARDO; PAVANI, RAPHAEL SOUZA; DA SILVA, MARCELO SANTOS; DE ARAUJO, CHRISTIANE BEZERRA; LIMA, ANDRE ARRUDA; AVILA, CARLA CRISTI; CESTARI, IGOR; MACHADO, CARLOS RENATO; ELIAS, MARIA CAROLINA. ATR Kinase Is a Crucial Player Mediating the DNA Damage Response in Trypanosoma brucei. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 8, DEC 22 2020. (17/18719-2, 18/12364-0, 15/10580-0, 14/02978-0, 14/24170-5, 19/01895-8, 16/50050-2, 14/13375-5)

PAVANI, RAPHAEL SOUZA; VITARELLI, MARCELA O.; FERNANDES, CARLOS A. H.; MATTIOLI, FABIO F.; MORONE, MARIANA; MENEZES, MILENE C.; FONTES, MARCOS R. M.; CANO, MARIA ISABEL N.; ELIAS, MARIA CAROLINA. Replication Protein A-1 Has a Preference for the Telomeric G-rich Sequence in Trypanosoma cruzi. Journal of Eukaryotic Microbiology, v. 65, n. 3, p. 345-356, MAY-JUN 2018. (14/02978-0, 15/10580-0, 13/07467-1)