Institute of molecular genetics (IGM)
Focus
FIS call: Dr. DANA BRANZEI awarded an advanced grant in the ERC Life Sciences sector
2023
With the publication of the rankings on 31 July, the evaluation procedure for the projects of the Italian Science Fund of the Ministry of University and Research, FIS 2021, was concluded. The FIS call aims to support fundamental research projects at national level, similar to those funded by the European Research Council (ERC).
Thanks to a budget of 50 million euro, 25 Advanced Grants were funded for amounts up to one and a half million euro each, intended for established Principal ...
SARS-CoV-2: danneggia il DNA e causa invecchiamento cellulare e infiammazione
2023
Ricercatori dell'IFOM di Milano e del CNR-IGM di Pavia hanno identificato le basi molecolari dell'aggressività e degli effetti deleteri di SARS-CoV-2: il virus provocherebbe danni al DNA della cellula e le impedirebbe di riparlarli, provocando così senescenza cellulare ed infiammazione cronica. Lo studio, pubblicato sull'autorevole rivista scientifica Nature Cell Biology, pone le premesse conoscitive per sviluppare in prospettiva nuovi trattamenti farmacologici che limitino gli effetti di ...
NOVEL STRATEGIES TO COUNTERACT OSTEOSARCOMA PROGRESSION
2021
A group of researchers from the Institute of Molecular Genetics of the National Research Council (IGM-CNR) lead by Dr. Vittoria Cenni, in collaboration with Dr. William Blalock and funded by the Italian Association of Cancer Research (AIRC), has discovered that the proliferation as well as the clonogenic potential of cells from osteosarcoma, a malignancy primarily afflicting children and young adults, can be tempered by the abrogation of the expression of the mechanotransducer protein ...
NEW CELLULAR FACTORS AND MECHANISMS CRUCIAL FOR DNA REPLICATION
2021
Three structural maintenance of chromosomes (SMC) complexes - cohesin, condensin and SMC5-SMC6 - are crucial for chromosome organization events in all domains of life. However, the roles of the Smc5/6 complex remain poorly understood, in spite of its association with human disease and cancers.
In a recent work, published in Nature Communications by researchers of IGM and IFOM, the authors identify that Smc5/6 roles in facilitating replication completion through difficult to replicate regions ...
New perspectives on the molecular mechanisms implicated in skin cancer development and skin photosensitivity
2021
Recent studies coordinated by Donata Orioli at the "Luigi Luca Cavalli-Sforza" Institute of Molecular Genetics of the CNR, in collaboration with international research Institutes and the University of Siena, identified a signalling pathway implicated in skin cancer development. The same group also identified new molecular alterations associated with skin photosensitivity.
The studies, supported by the AIRC Foundation for Cancer Research, were published in the Proc. Natl. Acad. Sci. USA e ...
From 3D chromatin structure to gene regulation
2021
A recent study coordinated by Francesco Ferrari - Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza" of the National Research Council in Pavia (IGM-CNR) and IFOM, the FIRC Institute of Molecular Oncology - demonstrated how the physical three-dimensional (3D) conformation of DNA inside the cell nucleus can be leveraged to reconstruct the network of regulatory interactions controlling genes activity.
The 3D organization of DNA and its associated proteins (chromatin) inside the cell ...
DDX11 loss causes replication stress and pharmacologically exploitable DNA repair defects
2021
Mutations in BRCA1 and BRCA2 tumor suppressor genes predispose individuals to breast and ovarian cancers. These cancers are treated in the clinic with platinum drugs and inhibitors of polyADP-ribose polymerase (PARP), which cause lesions requiring homologous recombination repair activities mediated by BRCA1 and BRCA2. However, BRCA1 and BRCA2 tumors often acquire resistance to chemotherapy, either by somatic reversion or by acquiring homologous recombination proficiency, leading to aggressive ...
A new mechanism to "starve" tumors
2021
In a study directed by Claudia Ghigna - Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza" of the National Research Council in Pavia (Cnr-Igm) - in collaboration with various Italian and international research groups, a novel protein variant expressed only on the surface of tumor blood vessels has been identified. The results of the study were published in Nature Communications.
The research shows how, through the mechanism known as 'alternative splicing', cells of the blood vessels ...
ERC Advanced Grant to Fabrizio d'Adda di Fagagna
2019
The prestigious ERC Advanced Grant was given to Fabrizio d'Adda di Fagagna, researcher of IGM-CNR of Pavia and IFOM of Milan specialized in response to DNA damage and cellular senescence. His pioneering research has already conquered in the past years another Advanced Grant and two Grants Proof of Concept, always destined by the European Commission to his particularly innovative and daring projects.
Discovering the laws of life: portraits by Redi, Maupertuis, Trembley, von Humboldt, Wallace, Mendel
2019
A new book by dr. Federico Focher entitled "Alla scoperta delle leggi della vita. Ritratti di Redi, Maupertuis, Trembley, Humboldt, Wallace, Mendel" was published (editor "Il prato").
Every scientific discovery, however revolutionary, is not born from nothing, but it is the last flower of a great tree, without which it would never have blossomed. Certainly you could just admire the cut flower, but only by knowing the leaves, the branch on which it shows itself, the tree as a whole, and the ...
FameLab Pavia: the winner is .... Matteo Cabrini
2019
Yesterday evening, 28th February 2019, the final selection of FameLab Pavia was held and the winner was Matteo Cabrini, a brilliant Post-Doc of the IGM-CNR who gave a presentation on Homeopathy.
FameLab Pavia was organized by INFN in collaboration with the Municipality of Pavia, IUSS University School of Pavia, EUCENTRE and the Institute of Molecular Genetics-CNR.
The compliments to Matteo and the second classified who spoke about biotechnology with an intervention on beer. But congratulations ...
Lo splicing alternativo che nutre il tumore
2019
Un gruppo di ricerca dell'Istituto di Genetica Molecolare del Consiglio Nazionale delle Ricerche (CNR-IGM) di Pavia guidato da Claudia Ghigna, sostenuto dall'AIRC-Associazione italiana per la ricerca contro il cancro e in collaborazione con il gruppo di Ugo Cavallaro dello IEO di Milano, ha scoperto che nei vasi sanguigni del tumore ovarico, una delle cause più comuni di morte per cancro nella popolazione femminile tra i 50 e i 69 anni, viene prodotta una nuova variante delle proteina L1, a cui ...
CNR and University in Pavia are allies in the fight against arbovirosis.
2019
Thanks to the generous contribution of Banca del Monte di Lombardia Foundation, a project aimed at developing a new strategy can start for fighting against viral diseases transmitted by mosquitoes. The project is based on a collaboration between the Molecular Virology Laboratory of the Molecular Genetics Institute "Luigi Luca Cavalli-Sforza" - CNR of Pavia, directed by Dr. Giovanni Maga, and the Laboratory of Insect Evolutionary Molecular Biology by Prof. Giuliano Gasperi and Prof. Anna ...
A New Strategy To Fight the West Nile Virus Infection
2019
A new family of DDX3X helicase inhibitors has been discovered to be effective in blocking West Nile virus replication in human cells without damaging healthy cells. The study conducted by research groups coordinated by Giovanni Maga (Institute of Molecular Genetics of the National Research Council of Pavia) and by Maurizio Botta (University of Siena), is published in the Journal of Medicinal Chemistry.
Brai A., Martelli F., Riva V., Garbelli A., Fazi R., Zamperini C. et al., DDX3X Helicase ...
A calendar to raiise funds for AIRC
2017
I volti delle donne" is a photo project ideated by Manuela Lanzafame, postdoc at the Institue of Molecular Genetics IGM-CNR of Pavia. Portraits of fourteen girls were used to describe different expression characterizing women and were used to realize a calendar. Earnings will be entirely devolved to the Italian foundation for cancer research (AIRC).
Non-coding RNA: the DNA damage fingerprints of cancer cells
2017
The integrity of our genome has to be maintained ed to prevent accumulation of harmful mutations, or cell death. This is even more needed in tumor cells where breaks in DNA occur at higher frequency. This feature of cancer cells can be exploited to set up therapeutic strategies based on inhibition of DNA repair with the aim to induce cell death. The drugs used so far to strike this "Achilles heel" of cancer cells block the enzymatic activity of essential DNA repair proteins, such as ATM, ATR or ...
Two genomic regions and lifestyle factors associated with human longevity.
2017
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. In a study, recently published in Nature Communications, a genome-wide association meta-analysis of 606,059 parents' survival, helped discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). Previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity have also been validated. Next, the study shows that giving up smoking, educational attainment, openness to new ...
Genome-wide association study identifies 74 loci associated with educational attainment
2016
Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample1, 2 of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide ...
"Free oxygen radicals and a hybrid genome: a dangerous cocktail"
2016
The genetic information is present in the cell as DNA, which is the form for storage and propagation to the next generation, and RNA, which is the form used by the cell to decode the instructions contained in its genes. DNA is composed of deoxynucleotides, while RNA is made of ribonucleotides. These two components are specifically recognised, respectively, by DNA polymerases, which use deoxynucleotides to build DNA, and by RNA polymerases, which synthesise RNA using ribonucleotides.
DNA ...
Alternative splicing and tumor
2016
The research group of Dr. Claudia Ghigna (Institute of Molecular Genetics of the National Research Council, CNR-IGM of Pavia) supported by the AIRC-Italian Cancer Research Association and in collaboration with the group of Dr. Ugo Cavallaro (IEO of Milan) showed that in the blood vessels of the ovarian tumor, one of the most common causes of death from cancer in the female population between 50 and 69 years, is present a new variant of the L1 protein. This variant (called L1-deltaTM) was ...
Two genomic regions and lifestyle factors associated with human longevity.
2016
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. In a study, recently published in Nature Communications, a genome-wide association meta-analysis of 606,059 parents' survival, helped discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). Previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity have also been validated. Next, the study shows that giving up smoking, educational attainment, openness to new ...
Microscopy School at the "Istituto Ortopedico Rizzoli" in Bologna
2016
The Microscopy School, in collaboration with the Digital Microscopy Center at "Istituto Ortopedico Rizzoli" in Bologna, aims to provide the basic information for the use of the main optical microscopy techniques such as SIM Super Resolution, STORM, STED , TIRF and deconvolution. Super resolution microscopy is one of the most significant developments in imaging in biology since the light microscope was invented.
The course is opened to researchers, students and technicians who are interested in ...
New Broad-spectrum antiviral agents open the way to a single drug effective against the most dangerous viruses
2016
The real possibility of a revolutionary approach to new-generation antivirals demonstrated by a study of the University of Siena and the Italian CNR.
A single drug against all viral infections, capable of hitting the protein that the virus uses to multiply. And this is the goal that will be made possible thanks to a study conducted in collaboration between the University of Siena and the CNR, which has identified new molecules capable of inhibiting the human protein DDX3. The research, ...
Sixth Arturo Falaschi Lecture
2016
As every year, the Institute of Molecular Genetics of CNR organized a conference to commemorate the scientific and human figure of Arturo Falaschi, first Director of the Institute and a great scholar of the mechanisms that govern DNA replication. This event is part of the IGM-CNR contribution to the Course of Doctorate in Genetics, Molecular and Cellular Biology, University of Pavia. The Sixth edition of the 'Arturo Falaschi Lecture' will be held by Professor Tomas Lindahl who, along with Paul ...
AIRC (Italian Association for Cancer Researchand) and young people
2016
AIRC rewards this year two young researchers at the IGM-CNR of Pavia: Elisa Belloni (with a three years fellowship) and Anna Di Matteo (with a one year fellowship). Both researchers are involved in a research project in the group directed by Dr. Claudia Ghigna aimed at identifying the molecular mechanisms driving the development of tumor vasculature, a fundamental process in cancer progression since cancerous cells stimulate the formation of new blood vessels in order to support their growth and ...
ARMENISE-HARVARD SUMMER FELLOWSHIPS
2016
We are all very proud that Sarah Giacchetti, LM student in Molecular Biology and Genetics, and Marco Roncandor, student in Medicine at the University of Pavia, have won one of the fellowships made available by the Giovanni Armenise-Harvard Foundation in collaboration with CNR, the College Ghislieri, CIBIO / University of Trento, the Scuola Normale and the Scuola Superiore Sant'Anna of Pisa.
Both winners are engaged in research work at our institute, Sarah Giacchetti at the Dr. Elena Botta's ...
IGM remember Dario Fo
2016
On October 13th, Dario Fo, Nobel Prize for Literature in 1997, died. Others may better illustrate his absolutely original and innovative contributions in the literature and in the performing and visual arts, as well as his passionate commitment to social issues. On our side, we would like to remember the enthusiastic support that he and his wife Franca dedicated to our scientific research, in particular to the project stemming from a collaboration between Giovanni Maga in our Institute and ...
Down syndrome: deficiencies in DNA repair of oxidative damage
2015
Down syndrome, also known as Trisomy 21, is associated, albeit with varying severity, with intellectual disability, premature aging, propensity to develop a disease similar to Alzheimer's, and the onset of some types of leukemia. Several studies have associated this phenotype with increased oxidative stress.
A research conducted by a team of IGM researchers coordinated by Ennio Prosperi, in collaboration with the Department of Pharmaceutical Sciences of the University of Pavia, have shown that ...
Environmental chemical agents and carcinogenesis
2015
The role of low doses of chemicals or chemical mixtures in carcinogenesis is still an open research field. On June 23rd of this year, the Journal Carcinogenesis published a special issue on this topic entitled "Assessing the Carcinogenic Potential of Low Dose Exposures to Chemical Mixtures in the Environment" (http://carcin.oxfordjournals.org/content/36/Suppl_1?etoc), result of the work of 174 researchers working on cancer research in several and prominent institutions all over the world. The ...
Tumors grow with the alternative splicing process
2015
Researchers at the Institute of Molecular Genetics of the CNR of Pavia, IFOM and the Department of Biosciences of the University of Milan, have shown that the protein Nova2, until now considered only present in the brain, is also expressed by the cells of the blood vessels and is directly related to their development. The study, published in Nature Communications, was supported by AIRC - Associazione Italiana per la Ricerca sul Cancro.
The formation of new blood vessels, a process called ...
Notch is a direct negative regulator of the DNA-damage response
2015
Il DNA è costantemente minacciato nella sua integrità. A proteggerlo o a rimediare quando viene danneggiato ci pensa il cosiddetto DNA damage response, che provvede a prevenire che venga danneggiato e a ripararlo se questo accade. Nella genesi tumorale l'attivazione di un oncogene è un evento necessario. In passato abbiamo scoperto che gli oncogeni danneggiano il DNA sottoponendolo ad una replicazione "eccessiva", non regolata e perciò prona alla rottura.
Abbiamo recentemente scoperto che un ...
Protecting the genome: a novel protein helps prevent DNA damage caused by free radicals.
2013
Macromolecules (DNA, proteins, and lipids) in all cells are constantly damaged by reactive oxygen species (ROS). In particular, ROS cause 1,000-7,000 DNA damages per day. Due to its lowest redox potential, the base guanine is mostly affected, resulting in the formation of 8-oxo-7,8-dihydroguanine. This modified base instructs incorporation of adenosine, instead of cytidine, by replicative DNA polymerases, potentially leading to GC ->TA transversion mutations. DNA polymerase lambda is the most ...
The life of neurons is not limited by genes
2013
The mammalian neurons can live as long as the body that has generated them. The limit of their existence would not, therefore, written in the genes. In practice, the brain can survive the body. This is demonstrated by an Italian experiment in which rat neurons were transplanted into the brain of a rat, where they set perfectly. The research was coordinated by the neurosurgeon Magrassi Lorenzo, who works at the University of Pavia, at the Fondazione Policlinico San Matteo and the lnstitute of ...
Platelet count is not equal for everybody
2013
It is time to rethink platelet count reference intervals actually used to define "normal" a person basing on his sex and age. A study recently published in PLOS ONE (http://dx.plos.org/10.1371/journal.pone.0054289) analyzed about 41.000 subjects involving 3 CNR Institutes and other research facilities, and showed that women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. Furthermore a ...
A possible role of DNA repair in the pathogenesis of Huntington's disease
2012
The Huntington's disease (Huntington's Disease, HD) is a hereditary nuerodegenerativa pathology, in which a particular sequence of three nucleotides (CAG), is "expanded", that is inserted in multiple copies at the beginning of the Huntingtin protein gene. When the number of these triplets exceeds a threshold value, the resulting protein in neurons assumes its pathological form, causing the degeneration of neurons. The mechanism by which the number of CAG triplets is expanded is not perfectly ...
Sla and cancer: a protein in a possible connection
2012
A joint study between IFOM (FIRC Institute of Molecular Oncology) in Milan and the Institute ofg Molecular Genetics - National Research Council (IGM-CNR) of Pavia, with the support of AIRC and Telethon, published in Cell, confirms the key role of senataxina in regulating the process of transcription and replication of DNA. Its mutation affects two serious neurodegenerative diseases and may play a role in cancer formation.
Reference: Chiara Lucca, Daniele Piccini, Walter Carotenuto, Marco ...
A new role for splicing factors in the DNA damage response.
2011
The cell response to endogenous DNA damage is still largely unexplored. The paper published on Nucleic Acids Research by Alessandra Montecucco laboratory demonstrates that splicing factor SRSF1 is hyper-phosphorylated in response to increased levels of replication-dependent DNA damage in DNA ligase I defective cells. This is accompanied by a change in alternative splicing events controlled by SRSF1 such as the production of Ron oncogene and caspase 9 alternative mRNAs. Both SRSF1 phosphorylation ...
Identification of the genes involved in the formation of platelets
2011
A large research project identifies 68 regions of the genome that regulate the formation and structure of the blood cells, affecting in many diseases. Millions of genetic variants were analyzed in 70,000 individuals. The study, carried out in collaboration between 100 research institutions, of which nine Italian, was published in Nature.
The joint efforts of researchers from four different continents, pertaining to one hundred research institutions, nine of which Italian, identify genetic ...
The cells recycle the byproducts of their metabolism to repair DNA
2011
Cellular DNA is constantly exposed to endogenous and exogenous damaging agents, such as free oxygen radicals, UV light and carcinogenic pollutants. The resulting chemical modifications of DNA bases, alter the genetic information contained in the cellular genome, causing mutations. Cells have evolved specialized enzymes, the so called translesion DNA polymerases, capable of retrieving the correct information from damaged DNA. Failure or misregulation of these mechanisms can lead to cancer. The ...
A tolerance pathway for oxidative DNA damage, common to humans and plants
2011
The study, published on the jorunal "Plant Cell", has been conducted by the DNA Enzymology team at the IGM-CNR, led by Dr. Giovanni Maga, together with the laboratory of Plant Molecular Biology of the University of Pavia, coordinated by Prof. Rino Cella. Oxidative stress, arising from either intracellular metabolism or exogenous sources (UV, radiations, pollution, smoking), can alter the chemical nature of DNA, inducing mutations. The group of Dr. Maga has previously published in the journal ...
A study of the Wiskott-Aldrich syndrome
2011
This work represents the most extensive data collection so far made regarding the hematopoietic stem cell transplantation in patients with Wiskott-Aldrich syndrome, a rare genetic disorder linked to the X chromosome that causes severe deficits on platelets as well as on of the immune system cells. The project has involved 12 of the most important American and European transplant centers, allowing the collection of data on transplantation and the subsequent follow-up of 194 patients ...
Smoking habits and DNA polymorphisms
2011
A study conducted by IGM-CNR researchers and published in the European Journal of Human Genetics, has established the importance of a human single-nucleotide polymorphisms (SNPs) in the human genome in the smoking behavior in the Italian population. In 2008, some studies had identified a biallelic variant present in the gene cluster CHRNA5-A3-B4 as associated to the smoker's addiction to large amounts of nicotine consumption (> 10 cigarettes per day). The same nucleotide variant has been ...
New mutations in the XPD gene in trichothiodystrophy patients
2009
Trichothiodystrophy (TTD) is a rare, autosomal recessive neurodevelopmental disorder most commonly caused by mutations in XPD, a gene that encodes a subunit of the transcription/repair factor TFIIH. The research group leaded by Miria Stefanini has recently characterised two new TTD cases showing moderate clinical features. Detailed biochemical and molecular investigations offered a clue to explain the clinical outcome of the patients and helped to shed light on the effect of specific mutations ...
Invisible nanoparticles fighting against dystrophy
2009
A study funded by Telethon and published in Molecular Therapy proposes the use of invisible nanoparticles in the fight against dystrophy. The work aims to convert the most severe form of muscular dystrophy, the Duchenne (DMD), in the slightest, the Becker dystrophy (DMB).
Eluding cell cycle checkpoints may represent a dangerous challenge for the organism: a model system helps us to investigate the strategies used by cells to cope with sustained levels of DNA damage however compatible with survival
2009
46BR.1G1 cells derive from a patient with a genetic syndrome characterized by drastically reduced replicative DNA ligase I (LigI) activity and delayed joining of Okazaki fragments. Here we show that the replication defect in 46BR.1G1 cells results in the accumulation of both single stranded and double stranded DNA breaks. This is accompanied by phosphorylation of the H2AX histone variant and the formation of γH2AX foci that mark damaged DNA. Single cell analysis demonstrates that the number ...
New insights on the action mechanisms of photodynamic therapy
2009
The paper, published on Histochemistry and Cell Biology - the official organ of the International Society for Histochemistry - refers to a research activity carried out since years at the IGM-CNR of Pavia in cooperation with the Department of Animal Biology of the University of Pavia, which focuses on the development of Photodynamic-Diagnosis/Therapy (PDD/T). This consists in a procedure of diagnosis and therapy of pathologies, in particular tumors, based on the activation of phototoxic ...
Ultrasonic and electromagnetic enhancement of a culture of human osteoblasts
2009
Several studies suggest that the surface coating of titanium could play an important role in bone tissue engineering. In the present study, we have followed a particular biomimetic strategy where ultrasonically or electromagnetically stimulated SAOS-2 human osteoblasts proliferated and built their extracellular matrix on a titanium surface. In comparison with control conditions, the ultrasonic and the electromagnetic stimulation caused higher cell proliferation, and increased surface coating ...
Further evidence of the relevance of unrepaired oxidative dna damage in precocious aging and neurodegeneration
2009
UV-sensitive syndrome (UVSS) is an autosomal recessive disorder characterised by sun-sensitivity and mild cutaneous symptoms resulting from defects in transcription-coupled repair (TC-NER), the sub-pathway of nucleotide excision repair that rapidly removes UV-induced damage from the transcribed strand of active genes. Cockayne syndrome (CS) is another genetic disorder defective in TC-NER showing developmental and neurological abnormalities and premature ageing. CS is caused by mutations in the ...
New Inhibitors of HIV-1 Replication
2008
HIV-1 replication has been inhibited by using a compound able to target the human cellular cofactor DEAD-box ATPase DDX3, essential for HIV-1 RNA nuclear export. This compound, identified by means of a computational protocol based on
pharmacophoric modeling and molecular docking calculations, represents the first
small molecule with such a mechanism of action and could lay the foundations for
a pioneering approach for the treatment of HIV-1 infections.
Maga G, Falchi F, Garbelli A, Belfiore ...
A new gene involved in Premature Ovarian Failure (POF)
2008
Premature Ovarian Failure (POF) is a disorder of women reproduction characterized by early onset of menopause (before 40 years of age). It is accompanied by severe problems of infertility and by cardiovascular and bone disorders. POF is a common disorder affecting about 1% of females worldwide. Despite its genetic component is demonstrated by the relevant portion of familial cases, few genes were found associated and the majority of genetic determinants are not known.
The new study, conducted ...
Myosclerosis myopathy is a collagen VI disorder
2008
Two patients belonging to a consanguineous family affected by myosclerosis myopathy were examined, screened for mutations of collagen VI genes, and studied by a detailed biochemical and morphological analysis of muscle biopsy and cultured skin fibroblasts.
We demonstrated that the patients had a novel homozygous nonsense COL6A2 mutation (Q819X); the mutated messenger RNA escaped nonsense-mediated decay and was translated into a truncated alpha2(VI) chain, lacking the sole C2 domain. As a ...
A new mechanism of tolerance to DNA oxidative damages in human cell
2008
The adenine misincorporated by replicative DNA polymerases (DNA pols) opposite 7,8-dihydro-8-oxoguanine (8-oxo-G) is removed by a specific glycosylase, leaving the lesion on the DNA. Subsequent incorporation of C opposite 8-oxo-G on the resulting one nucleotide gapped DNA is essential for the removal of the 8-oxo-G to prevent G-C to T-A transversion mutations. By using model DNA templates, purified DNA pols beta and lambda and knockout cell extracts, we show here that the auxiliary proteins ...
H2AX histone is involved in DNA repair
2008
In mammalian cells, the H2AX histone is rapidly phosphorylated upon the induction of DNA double strand breaks and promotes their repair, which is required for preserving genomic integrity. Etoposide is an inhibitor of DNA topoisomerase II, which causes DNA breaks and induces H2AX phosphorylation. To elucidate whether H2AX may affect cellular sensitivity to etoposide, we studied the response to this agent in immortalized embryonic fibroblasts derived from H2AX knockout mice. Clonogenic assays in ...
Autofluorescence as an intrinsic parameter of cell and tissue suitable for diagnostic purposes
2003
Most of the substances involved both in the organization and the
functional-metabolic aspects of biological material can act as
fluorophores, giving rise to a fluorescence emission under excitation at
suitable wavelengths. The properties of this fluorescence signal are
strictly related to the chemical nature and the concentration of the
endogenous fluorophores, to their distribution inside the biological
substrate, and to the physico-chemical characteristics of their
microenvironment. On ...
Enzymes working at replication factories
2002
The survival of organisms depends on the accurate transmission of the genetic information from one cell to its daughters through a metabolic pathway called DNA replication. DNA replication occurs in vivo in an ordered and highly organized way to satisfy three main tasks:
1) DNA replication must occur in a specific moment of the cell cycle called S phase or synthesis phase
2) each DNA sequence must be duplicated once per cell cycle
3) the genetic information (determined by the nucleotide ...
Autofluorescence-based optical biopsy
2002
Autofluorescence as an intrinsic parameter of cell and tissue suitable
for non-invasive, real-time diagnostic techniques.
Most of the substances involved both in the organization and the
functional-metabolic aspects of biological material can act as
fluorophores, giving rise to a fluorescence emission under excitation at
suitable wavelengths. The properties of this fluorescence signal are
strictly related to the chemical nature and the concentration of the
endogenous fluorophores, to their ...