A5025609663- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Advanced biosensing and bioanalysis techniques
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- Carcinogens and Genotoxicity Assessment
- Nematode management and characterization studies
- Cancer-related gene regulation
- Chromatin Remodeling and Cancer
- Radiation Therapy and Dosimetry
- Nuclear Structure and Function
- International Maritime Law Issues
- Acute Lymphoblastic Leukemia research
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Pluripotent Stem Cells Research
- Folate and B Vitamins Research
- Evolution and Genetic Dynamics
Sapienza University of Rome
2020-2025
Rockefeller University
2017-2023
Istituto Pasteur
2020
Commonwealth Scientific and Industrial Research Organisation
2013
University of Cambridge
2010-2011
The Gurdon Institute
2010
Wellcome Trust
2010
Brunel University of London
2009
The signaling cascade initiated in response to DNA double-strand breaks (DSBs) has been extensively investigated interphase cells. Here, we show that mitotic cells treated with DSB-inducing agents activate a “primary” damage (DDR) comprised of early events, including activation the protein kinases ataxia telangiectasia mutated (ATM) and DNA-dependent kinase (DNA-PK), histone H2AX phosphorylation together recruitment mediator checkpoint 1 (MDC1), Mre11–Rad50–Nbs1 (MRN) complex sites. However,...
Significance The molecular basis of immunodeficiency–centromeric instability–facial anomalies (ICF) syndrome is poorly understood. ICF caused by mutations in HELLS, CDCA7, or the DNA methyltransferase DNMT3b. While these all cause methylation defects, little known about function CDCA7. It has been speculated that which belongs to SNF2 family ATPase, facilitates DNMT3b through nucleosome remodeling, but HELLS on its own fails exhibit such an activity. Here, starting from a comparative...
Significance The centromere is a highly specialized genomic locus playing critical role in chromosome segregation during cell division and made of characteristic repetitive DNA sequences. Due to their nature, it has been difficult study the organization human centromeres. Here, we present way monitor stability centromeres using chromosome-orientation fluorescent situ hybridization superresolution microscopy. We show that centromere-specific histone variant CENP-A centromere-associated...
Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of centromere-specific histone H3 variant CENP-A in safeguarding replication alpha-satellite repeats structural aneuploidy. Rapid removal S phase, but not other cell-cycle stages, caused accumulation R...
Centromeres are chromosomal loci that ensure proper chromosome segregation by providing a platform for kinetochore assembly and spindle force transduction during cell division. Human centromeres defined primarily unique chromatin domain featuring the histone H3 variant, Centromere Protein A (CENP-A), marks single active centromere locus per chromosome. CENP-A typically occupies small subregion of low DNA methylation within multi-megabase arrays hypermethylated alpha-satellite repeats...
Spaceflight imposes unique stressors that disrupt mitochondrial function, vital for energy production and immune regulation. Our multi-omics analysis (proteomics, bisulfite sequencing, RNA-seq, single-nuclei RNA/ATAC-seq) on astronauts, rodents, model organisms (flies, worms, plants) revealed progressive impairment of oxidative phosphorylation (OXPHOS) during spaceflight, with delayed recovery post-return across species. In radiation ≥10.34 mGy activated persistent stress pathways multiple...
DNA double-strand breaks (DSBs) are extremely cytotoxic with a single unrepaired DSB being sufficient to induce cell death. A complex signalling cascade, termed the damage response (DDR), is in place deal such lesions and maintain genome stability. Recent work by us others has found that cascade activated DSBs mitosis truncated, displaying apical, but not downstream, components of DDR. The E3 Ubiquitin ligases RNF8, RNF168 BRCA1, along DDR mediator 53BP1, recruited sites mitosis, activation...
Common fragile sites (CFSs) are particularly vulnerable regions of the genome that become visible as breaks, gaps, or constrictions on metaphase chromosomes when cells under replicative stress. Impairment in DNA replication, late replication timing, enrichment A/T nucleotides tend to form secondary structures, paucity active inducible origins, generation R-loops, and collision between transcription machineries long genes some reported characteristics CFSs may contribute their tissue-specific...
Abstract Replication stress (RS) is a leading cause of genome instability and cancer development. A substantial source endogenous RS originates from the encounter between transcription replication machineries operating on same DNA template. This occurs predominantly under specific contexts, such as oncogene activation, metabolic stress, or deficiency in proteins that specifically act to prevent resolve those transcription-replication conflicts (TRCs). One protein Senataxin (SETX), an RNA:DNA...
The human centromere comprises large arrays of repetitive α-satellite DNA at the primary constriction mitotic chromosomes. In addition, centromeres are epigenetically specified by centromere-specific histone H3 variant CENP-A that supports kinetochore assembly to enable chromosome segregation. Because is bound only a fraction elements within megabase-sized DNA, correlating three-dimensional (3D) organization and remains elusive. To visualize single chromatid, we used combination orientation...
Human centromeres are composed of large tandem arrays repetitive alpha satellite DNA, which often sites aberrant rearrangement in cancers (Mitelman et al., 1997;Padilla-Nash 2001).To date, annotation the human centromere sequences remains incomplete, greatly hindering in-depth functional studies these regions essential for chromosome segregation.In order to monitor sister chromatid exchange happening at (C-SCE) due recombination and mutagenic events, I have applied Chromosome-Orientation...
Abstract Histone post-translational modifications promote a chromatin environment that controls transcription, DNA replication and repair, but surprisingly few phosphorylations have been documented. We report the discovery of histone H3 serine-57 phosphorylation (H3S57ph) show it is implicated in different repair pathways from fungi to vertebrates. identified CHK1 as major human H3S57 kinase, disrupting or constitutively mimicking H3S57ph had opposing effects on rate recovery stress, 53BP1...
Comparative analysis of recent human genome assemblies highlights profound sequence divergence that peaks within polymorphic loci such as centromeres. This raises the question about adequacy relying on reference genomes to accurately analyze sequencing data derived from experimental cell lines. Here, we generated complete diploid assembly for retinal epithelial cells (RPE-1), a widely used non-cancer laboratory line with stable karyotype, use matched multi-omics analysis. Our RPE1v1.0...