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Characterization of the proteins LmRad9 and LmRad1 in the DNA damage response of Leishmania major

Grant number: 14/06824-8
Support Opportunities:Regular Research Grants
Duration: October 01, 2014 - December 31, 2016
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Luiz Ricardo Orsini Tosi
Grantee:Luiz Ricardo Orsini Tosi
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Our laboratory investigates the expression and function of the protein complex 9-1-1 (Rad9-Rad1-Hus1) in the DNA Damage Response (DDR) of the protozoan parasite Leishmania. In other eukaryotes this complex acts in the sensing of DNA Damage and in the signaling required for cell cycle arrest and proper DNA repair. We have shown that the Hus1 homologue in the parasite participates in the DDR and also interacts with a Rad9 homologue in vivo. Both, LmHus1 and LmRad9 also participate in telomere maintenance. We showed that LmHus1 deficiency interfered with a proper replicative stress checkpoint. We also demonstrated that LmHus1 is well conserved in the eukaryote lineage, while LmRad9 presents a much lower conservation. Moreover, the parasite genome does not seem to encode a Rad1 homologue. These data suggest a peculiar mechanism for the detection and signaling of DNA Damage. The study of this complex in Leishmania will contribute to the understanding not only of the parasite genome homeostasis, but also, of the evolution of the DDR in eukaryotes. Therefore, the aim of this proposal is (i) to identify the possible homologue of Rad1 in L. major; (ii) study the expression and function if its product; (iii) investigate the architecture of the 9-1-1 complex in the parasite; and (iv) expand the functional characterization of the proteins LmHus1 and LmRad9. (AU)

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Scientific publications (5)
(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)
DAMASCENO, JEZIEL D.; SILVA, GABRIEL L. A.; TSCHUDI, CHRISTIAN; TOSI, LUIZ R. O.. Evidence for regulated expression of Telomeric Repeat-containing RNAs (TERRA) in parasitic trypanosomatids. Memórias do Instituto Oswaldo Cruz, v. 112, n. 8, p. 572-576, . (14/06824-8, 13/00570-1)
SANTOS, RENATO E. R. S.; SILVA, GABRIEL L. A.; SANTOS, ELAINE V.; DUNCAN, SAMUEL M.; MOTTRAM, JEREMY C.; DAMASCENO, JEZIEL D.; TOSI, LUIZ R. O.. A DiCre recombinase-based system for inducible expression in Leishmania major. Molecular and Biochemical Parasitology, v. 216, p. 45-48, . (14/00751-9, 13/26806-1, 14/06824-8, 13/00570-1, 09/54014-7)
DAMASCENO, JEZIEL D.; OBONAGA, RICARDO; SILVA, GABRIEL L. A.; REIS-CUNHA, JOAO L.; DUNCAN, SAMUEL M.; BARTHOLOMEU, DANIELLA C.; MOTTRAM, JEREMY C.; MCCULLOCH, RICHARD; TOSI, LUIZ R. O.. Conditional genome engineering reveals canonical and divergent roles for the Hus1 component of the 9-1-1 complex in the maintenance of the plastic genome of Leishmania. Nucleic Acids Research, v. 46, n. 22, p. 11835-11846, . (14/00751-9, 17/07092-9, 14/06824-8, 13/00570-1, 16/16454-9, 16/50050-2)
DAMASCENO, JEZIEL D.; OBONAGA, RICARDO; SANTOS, ELAINE V.; SCOTT, ALAN; MCCULLOCH, RICHARD; TOSI, LUIZ R. O.. Functional compartmentalization of Rad9 and Hus1 reveals diverse assembly of the 9-1-1 complex components during the DNA damage response in Leishmania. Molecular Microbiology, v. 101, n. 6, p. 1054-1068, . (13/00570-1, 14/00751-9, 13/26806-1, 14/06824-8, 09/54014-7)
DAMASCENO, JEZIEL D.; SILVA, GABRIEL L. A.; TSCHUDI, CHRISTIAN; TOSI, LUIZ R. O.. Evidence for regulated expression of Telomeric Repeat-containing RNAs (TERRA) in parasitic trypanosomatids. Memórias do Instituto Oswaldo Cruz, v. 112, n. 8, p. 5-pg., . (13/00570-1, 14/06824-8)

Please report errors in scientific publications list by writing to: gei-bv@fapesp.br.