INFORMAZIONI SU

CORTOLEZZIS YLENIA

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Supervisori: prof. Xodo e Dr. Di Giorgio

Identification of the epigenetic regulators monitoring the folding of DNA and RNA in non-canonical structures during oncogenesis

Genomic instability plays a key role in supporting carcinogenesis. Non-canonical DNA and RNA structures affect genome stability and gene expression. Among them, DNA and RNA G-quadruplex (G4s) are constituted of stacked guanine tetrads held by Hoogsteen hydrogen bonds and stabilized by monovalent metal cations. G4s were proven to regulate telomeres stability and the transcription of oncogenes, like c-MYC, NRAS, HRAS and KRAS, thus playing a role in sustaining oncogenesis. At the level of G-rich histone-depleted regulative elements, three-stranded DNA-RNA hybrids, called R-loops, frequently co-occur with G4s and they also act on genome stability and DNA replication. The aim of this project is to identify the epigenetic regulators that promote or prevent the formation of G4s and R-loops in absence or presence of exogenously induced DSBs. Moreover, we aim to investigate the impact of G4s and R-loops on replication fork progression, HR-repair proteins loading and RNA Pol II processivity.