Alessandra Pelegrini

From Laboratório de Reparo de DNA

BSc, Biological Sciences, Universidade Federal do Rio Grande do Sul – UFRGS,(2001/2005).
MSc, Celular and Molecular Biology, Universidade Federal do Rio Grande do Sul – UFRGS, (2006/2007).
PhD, Celular and Molecular Biology, Universidade Federal do Rio Grande do Sul - UFRGS and Universidade de São Paulo – USP, ( 2007/2012).
Post-doctoral Fellowship, Cancer Research Center of Toulouse – CRCT (2016/2018)
Post-doctoral Fellowship in DNA Repair Lab - Institute of Biological Sciences at University of São Paulo - USP (2013 – Current)

The researcher has experience in cell and molecular biology, culture of human and animal cells, proteomics and mass spectrometry, microscopy and immunofluorescence, drug testing and cytotoxicity

Research keywords: Cancer, DNA repair, Replicative stress, Genetic instability and Chemotherapy and Therapeutic resistance

Contato: aleepelegrini[at]

Current Project

Cancer is currently the leading cause of morbidity and mortality worldwide which it is characterized by abnormal and uncontrolled cell growth in addition to genetic instability. It is very likely that genetic instability accelerates and even possibly initiates the proliferation of cancer cells by favoring the emergence of variant cells. Indeed, alterations of genes involved in genome maintenance promote carcinogenesis. This process is predominantly generated in S phase, during the DNA synthesis and relies on a replication stress activated by oncogenes. During the replication, the fork can be stalled for several reasons, such as DNA damage, structured DNA, nucleotide depletion and encounters with the transcription machinery, characterizing replication stress. In this way, replication stress contributes to chromosomal instability since stalled forks may eventually collapse, producing a broken DNA end. Up until recently, the mechanisms leading to fork collapse were only described after prolonged exposition of DNA replication stress sources (24 hours) by Mus81 activity. However, we have been described a phenomenon in which DNA replication forks stalls in response to DNA replication stress and are rapidly converted into DSBs, which we refer to as rapid replication fork breakage (RRFB) and it is dependent of XPF and Artemis nucleases. In this project, i have investigated the role of that endonuclease and its partner, ERCC1, in interstrand crosslink (ICLs) repair and its evolvement in chemotherapy sensitivity. Since the ICLs may cause persistent fork stalling, the proposed objective for this research is understanding how the XPF-ERCC1 complex and each of these separate protein participate in DNA replication stress, exploring their roles from the regulation of fork collapse to repair mechanisms, and evaluating the importance of these early events in the development of genetic instability from chromosomal aberrations.

Articles Published in Scientific Journals

Melo-Hanchuk TD, Slepick PF, Meirelles GV, Basei FL, Lovato DV, Granato DC, Pauletti BA, Domingues RR, Leme AFP, Pelegrini AL, Lenz G, Knapp S, Elkins JM and Kobarg J. NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin. Scientific Reports 2017; 7: (5445) 1-13.

Filippi-Chiela EC, Thomé MP, Bueno e Silva MM, Pelegrini AL, Ledur PF, Garicochea B, Zamin LL, Lenz G. Resveratrol abrogates the temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the temozolomide-induced senescence in glioma cells. BMC Cancer 2013; 13: 147.

Lopez PL, Filippi-Chiela EC, Silva AO, Cordero EA, Garcia-Santos D, Pelegrini AL, Reder GM, Barbieri NL, Lenz G. Sensitization of glioma cells by x-linked inhibitor of apoptosis protein knockdown. Oncology 2012; 83: 75-82.

Pelegrini AL, Moura DJ, Brenner BL, Ledur PF, Maques GP, Henriques JA, Saffi J, Lenz G. Nek1 silencing slows down DNA repair and blocks DNA damage-induced cell cycle arrest. Mutagenesis 2010; 25: 447-54.

Gerhardt D, Horn AP, Gaelzer MM, Frozza RL, Delgado-Cañedo A, Pelegrini AL, Henriques AT, Lenz G, Salbego C. Boldine: a potential new antiproliferative drug against glioma cell lines. Invest New Drugs 2009; 27, 517-25.

Ferramentas pessoais