A5005467171- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- PARP inhibition in cancer therapy
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Free Radicals and Antioxidants
- Metal complexes synthesis and properties
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
Linköping University
2024-2025
Istituto di Genetica Molecolare
2024
Sapienza University of Rome
2019-2023
Abstract Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Here we found that poly (ADP-ribose) polymerase 1 (PARP1) interacts covalently PARylates in S-phase modifying its affinity. Therefore, genetic pharmacological inhibition of PARP1 impairs the dynamic association bromodeoxyuridine...
Abstract During classical non-homologous end joining (cNHEJ), DNA-dependent protein kinase (DNA-PK) encapsulates free DNA ends, forming a recruitment platform for downstream end-joining factors including ligase 4 (LIG4) 1 . DNA-PK can also bind telomeres and regulate their resection 2–4 , but does not initiate cNHEJ at this position. How the process is regulated in context-specific manner currently unclear. Here we show that shelterin components TRF2 RAP1 form complex with directly represses...
BRCA1/2 are tumor suppressor genes controlling genomic stability also at telomeric and subtelomeric loci. Their mutation confers a predisposition to different human cancers but sensitivity antitumor drugs including poly(ADP-ribose) polymerase (PARP) inhibitors G-quadruplex stabilizers. Here we demonstrate that BRCA2 deletion triggers TERRA hyperexpression alternative lengthening mechanisms (ALT) in colon cancer cells presence of telomerase activity. This finding opens the question if...
Human apolipoprotein E (APOE) is a crucial lipid transport glycoprotein involved in various biological processes, including metabolism, immune response, and neurodegeneration. Elevated APOE levels are linked to poor prognosis several cancers increased risk of Alzheimer's disease (AD). Therefore, modulating expression presents promising therapeutic strategy for both cancer AD. Considering the pivotal role G-quadruplex (G4) structures medicinal chemistry as modulators gene expression, here, we...
Human Apolipoprotein E (APOE) is a crucial lipid transport glycoprotein involved in various biological processes, including metabolism, immune response, and neurodegeneration. Elevated APOE levels are linked to poor prognosis several cancers increased risk of Alzheimer's disease (AD). Therefore, modulating expression presents promising therapeutic strategy for both cancer AD. Considering the pivotal role G-quadruplex (G4) structures medicinal chemistry as modulators gene expression, here we...
During classical non-homologous end joining (cNHEJ), DNA-dependent protein kinase (DNA-PK) encapsulates free DNA ends, forming a recruitment platform for downstream end-joining factors including Ligase 4 (LIG4) 1 . DNA-PK can also bind telomeres and regulate their resection 2–4 , but does not initiate cNHEJ at this position. How the process is regulated in context-specific manner currently unclear. Here we show that shelterin components TRF2 RAP1 form complex with directly represses its...
Abstract Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Poly (ADP-ribose) polymerase 1 (PARP1) chromatin associated enzyme which adds poly polymers (PARs) to acceptor proteins covalent hetero-modification. Here we found that covalently PARylated PARP1 during synthesis. downregulation...