T: : he tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage : Abstract : Nature. Nature 399, 806-809 (24 June 1999) | doi:10.1038/21690; Received 21 April 1999; Accepted 6 May 1999 JianGen Gong1,5, Antonio Costanzo5,2, Hong-Qiong Yang1, Gerry Melino3, William G.
Kaelin, Jnr4, Massimo Levrero2 & Jean Y. J. Wang1 Department of Biology and the Cancer Center, University of California, San Diego, La Jolla, California 92093-0322, USA Laboratory of Gene Expression, Fondazione A Cesalpino, University of Rome La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy Biochemistry Laboratory, Istituto Dermopatico dell'Immacolata-IRCCS, Department of Experimental Medicine, University of Rome Tor Vergata 00133, Rome, Italy Howard Hughes Medical Institute, and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA These authors contributed equally to this work Top of page Cancer chemotherapeutic agents such as cisplatin exert their cytotoxic effect by inducing DNA damage and activating programmed cell death (apoptosis).
EpigeneticsCourseranotes. Non-coding RNAs in Colorectal Cancer. Chromatin Remodeling and the Control of Gene Expression. Carl Wu‡ + Author Affiliations Biochemical and genetic findings accumulated over the past decade have established that the condensation of eukaryotic DNA in chromatin functions not only to constrain the genome within the boundaries of the cell nucleus but also to suppress gene activity in a general manner.
This genetic repression extends from the level of the nucleosome, the primary unit of chromatin organization, where coiling of DNA on the surface of the nucleosome core particle impedes access to the transcriptional apparatus, to the higher order folding of nucleosome arrays and the organization of silent regions of chromatin (for reviews see Refs. 1-6 and 105). Chromatin structure is inextricably linked to transcriptional regulation, and recent studies show how chromatin is perturbed so as to facilitate transcription (for reviews see Refs. 7-12). Histone Acetylation Tetrahymena Histone Acetyltransferase A and Yeast Gcn5. 20130467. Kiyoshi Nagai - MRC Laboratory of Molecular Biology. The removal of introns from nuclear pre-mRNA and splicing together of exons into a continuous translatable coding sequence is catalyzed by a large and dynamic RNA-protein machine known as the spliceosome.
Five small nuclear ribonucleoprotein particles (U1, U2, U4/U6 and U5 snRNPs) and numerous non-snRNP factors assemble at each intron in the pre-mRNA to form a spliceosome. Subsequently the spliceosome undergoes extensive compositional and structural changes to become catalytically active. How does the spliceosome assemble and carry out its function? How did a molecular machine as immense and complex as the spliceosome evolve in the Eukaryotic lineage? Our project aims to answer these questions by solving structures of the whole spliceosome and its key components by crystallography and electron cryo-microscopy (cryoEM).
British Society for Gene and Cell Therapy. Spindle transfer for Mitochondrial Replacement Therapy. This article from the Mitalipov group (Kang et al. 2016) came out at a particularly interesting time, since it followed closely on the report from a US-based team in Mexico on the successful birth of a baby to a mother with the mitochondrial mutation causing Leigh syndrome, which had been corrected by transfer of maternal nuclear DNA to a donor oocyte (Hamzelou 2016).
It was also published on the same day as the decision by the HFEA that clinics are now free to apply for permission to carry out mitochondrial replacement, with the first patients expected to be seen as early as Spring 2017 (Forster 2016). The paper from Kang et al., (2016) details studies performed with oocytes from four families with Leigh syndrome and one with MELAS, both associated with mutations in mitochondrial DNA (mtDNA). Characterisation of the mtDNA burden in tissues from the patients and their children highlighted the problem with genetic testing for this condition. References. Dr Luca Magnani. Summary Cancer cells exhibit altered transcriptional profiles when compared to their tissue of origin.
Genetic alterations participate in promoting defective transcription, however they don't explain the full spectrum of aberrations found in malignant tissues. Gene expression is also controlled via modifications of the chromatin landscape including DNA methylation, histone modifications and chromatin remodelling.
Our objective is to characterize the role of the chromatin landcape in oncogenesis. A second goal is to understand how cancer cells reprogram the chromatin landscape to escape treatment. We have used breast cancer models to demonstrate that epigenetic reprogramming of the chromatin landscape promotes the expression of genes directly related to resistance to endocrine therapies. My lab is also interested in understanding the extent of interactions existing between genetic and epigenetic alterations.
Dahlman J Nat Biotechnol 2015.