How do checkpoint proteins Rad9 and Hus1 act to maintain genome stability in the protozoan Leishmania major?

• Grant number: 17/07092-9
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2017
• End date: February 29, 2020
• 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 has contributed to the understanding of DNA damage signaling pathways in the protozoan parasite Leishmania. The study of the detection and signaling of DNA damage in an early-diverging eukaryote can further our understanding of how DNA Damage Response (DDR) has been established in the eukaryotic line. Based on the identification and characterization of checkpoint proteins Rad9 and Hus1 in Leishmania, reported by our group, we intend to investigate the involvement of these proteins in more specific aspects of the peculiar biology of these organisms. Thus, the general objective of this proposal is (i) to use deficient or null cell lines for Rad9 or Hus1 to characterize the role of these proteins in the control of copy numbers in the L. major genome; (ii) to use ChIP and ChIP-seq to investigate the complexes containing Hus1 or Rad9 and the loci to which Hus1 associates in L. major in response to replicative stress; and (iii) to use truncated versions of Rad9 from L. major to characterize the role of its C-terminal domain. (AU)

Scientific publications

(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 DENER; MARQUES, CATARINA A.; BERALDI, DARIO; CROUCH, KATHRYN; LAPSLEY, CRAIG; OBONAGA, RICARDO; TOSI, LUIZ R. O.; MCCULLOCH, RICHARD. Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication. eLIFE, v. 9, SEP 8 2020. (17/07092-9)

PASSOS SILVA, DANIELLE GOMES; SANTOS, SELMA DA SILVA; NARDELLI, SHEILA C.; MENDES, ISABELA CECILIA; GUIMARAES FREIRE, ANNA CLAUDIA; REPOLES, BRUNO MARCAL; RESENDE, BRUNO CARVALHO; COSTA-SILVA, HELLIDA MARINA; DA SILVA, VERONICA SANTANA; DE OLIVEIRA, KARLA ANDRADE; et al. The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions. PLoS Neglected Tropical Diseases, v. 12, n. 11, NOV 2018. (17/07092-9)

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, DEC 14 2018. (14/00751-9, 17/07092-9, 14/06824-8, 13/00570-1, 16/16454-9, 16/50050-2)