SPADAFORA LINE-1-mediated chromatin remodeling of cancer cells (DSB.AD007.219)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of Traslational Pharmacology (IFT)

Other structures collaborating in the research project

• Institute of molecular biology and pathology (IBPM)

Project manager

CORRADO SPADAFORA
Phone number: 0649934486
Email: CORRADO.SPADAFORA@IFT.CNR.IT

Abstract

§ Abstract: Earlier work showed that reverse transcriptase (RT) inhibitors decrease the proliferation rate of cancer cells while non-cancer cells show limited sensitivity: this highlights the suitability of RT inhibitors as cancer-selective inhibitory drugs. Our results also revealed that RT inhibitors cause a remodeling of nuclear architecture in cancer cells, the induction of genome damage, alteration of the peripheral heterochromatin and fragmentation of the nuclear lamina. To clarify the mechanisms governed by RT inhibitors, we propose to investigate the subcellular localization and molecular interactors of RT-containing LINE-1 ORF2p. More specifically, we plan to localize ORF2p at peripheral heterochromatin, to assess its physical interaction with g-H2AX (DNA damage-specific histone variant) and with lamin B1 which undergoes fragmentation. This work sheds mechanistic light on RT inhibitors as cancer therapeutic drugs

Goals

ND

Start date of activity

13/05/2020

Keywords

LINE-1 RT, chromatin, cancer

Last update: 16/05/2024