Characterization of HJURP protein-protein interaction-networks in glioma cells submitted to different types of DNA damage

• Grant number: 19/24335-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): March 09, 2020
• Effective date (End): March 08, 2021
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Valeria Valente
• Grantee: Rodrigo de Almeida
• Supervisor: Wolf-Dietrich Heyer
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Research place: University of California, Davis (UC Davis), United States
• Associated to the scholarship: 17/15208-7 - Investigation of HJURP functions in the acquisition of stemness in glioblastoma lines, BP.DR

Abstract

The Holliday Junction Recognizing Protein (HJURP) is overexpressed in many tumors and also correlated with poor prognosis. HJURP has a well-described activity as the CENP-A chaperone and promotes CENP-A deposition at centromeres. Our group has been studying the participation of HJURP in the DNA double-strand break (DSB) repair of glioma cells. We observed that HJURP is recruited to DNA damage sites, promotes chromatin relaxation and favors restoration of radiation-induced DSBs and the overall activity of the homologous recombination (HR) pathway. Beside this, HJURP promotes an increase in proliferation of glioblastoma cell lines and favors the repair of DNA lesions resulting from replicative stress. We also found a strong correlation of HJURP expression and the proliferative indexes of tumor samples from public database and identified several genes involved in cell cycle control, Fanconi Anemia and homologous recombination pathways, co-expressed with HJURP in astrocytomas. Altogether, this data suggests the participation of HJURP in control of replicative stress, chromosome stability and cancer development. So, in this project we intend to perform experiments of immunoprecipitation, mass spectrometry and bioinformatic analysis to investigate which proteins interact with HJURP in different cellular contexts: i) normal and cancer cells with basal HJURP expression and with exogenous HJURP induction, ii) cells with DNA damage induced by radiation, iii) and cells with damage induced by drugs that mimics replication stress. The generation of these pieces of data will enable us to make a considerable progress in the understanding of new HJURP functions, not yet described.

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)

SERAFIM, RODOLFO BORTOLOZO; DA SILVA, PATRICK; CARDOSO, CIBELE; DI CRISTOFARO, LUIS FERNANDO MACEDO; NETTO, RENATO PETITTO; DE ALMEIDA, RODRIGO; NAVEGANTE, GEOVANA; STORTI, CAMILA BALDIN; DE SOUSA, JULIANA FERREIRA; DE SOUZA, FELIPE CANTO; et al. Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation. FRONTIERS IN ONCOLOGY, v. 11, MAY 25 2021. (13/08135-2, 18/05018-9, 13/13465-1, 19/24335-8, 18/22799-4, 16/12744-2, 17/15208-7)