Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2011-02-05
    Description: p53-binding protein 1 (53BP1) is known to be an important mediator of the DNA damage response, with dimethylation of histone H4 lysine 20 (H4K20me2) critical to the recruitment of 53BP1 to double-strand breaks (DSBs). However, it is not clear how 53BP1 is specifically targeted to the sites of DNA damage, as the overall level of H4K20me2 does not seem to increase following DNA damage. It has been proposed that DNA breaks may cause exposure of methylated H4K20 previously buried within the chromosome; however, experimental evidence for such a model is lacking. Here we found that H4K20 methylation actually increases locally upon the induction of DSBs and that methylation of H4K20 at DSBs is mediated by the histone methyltransferase MMSET (also known as NSD2 or WHSC1) in mammals. Downregulation of MMSET significantly decreases H4K20 methylation at DSBs and the subsequent accumulation of 53BP1. Furthermore, we found that the recruitment of MMSET to DSBs requires the gammaH2AX-MDC1 pathway; specifically, the interaction between the MDC1 BRCT domain and phosphorylated Ser 102 of MMSET. Thus, we propose that a pathway involving gammaH2AX-MDC1-MMSET regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates 53BP1 recruitment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064261/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064261/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pei, Huadong -- Zhang, Lindsey -- Luo, Kuntian -- Qin, Yuxin -- Chesi, Marta -- Fei, Frances -- Bergsagel, P Leif -- Wang, Liewei -- You, Zhongsheng -- Lou, Zhenkun -- CA130996/CA/NCI NIH HHS/ -- CA151329/CA/NCI NIH HHS/ -- R01 AG020686/AG/NIA NIH HHS/ -- R01 AG020686-06A2/AG/NIA NIH HHS/ -- R01 AG020686-07/AG/NIA NIH HHS/ -- R01 CA130996/CA/NCI NIH HHS/ -- R01 CA130996-03/CA/NCI NIH HHS/ -- R01 CA133966/CA/NCI NIH HHS/ -- R01 CA133966-01A2/CA/NCI NIH HHS/ -- R01 CA133966-02/CA/NCI NIH HHS/ -- R01 CA133966-03/CA/NCI NIH HHS/ -- R01 CA136671/CA/NCI NIH HHS/ -- R01 CA136671-02/CA/NCI NIH HHS/ -- R01 CA136671-03/CA/NCI NIH HHS/ -- R01 CA151329/CA/NCI NIH HHS/ -- R01 CA151329-01/CA/NCI NIH HHS/ -- R56 AG020686/AG/NIA NIH HHS/ -- R56 AG020686-06A1/AG/NIA NIH HHS/ -- England -- Nature. 2011 Feb 3;470(7332):124-8. doi: 10.1038/nature09658.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21293379" target="_blank"〉PubMed〈/a〉
    Keywords: Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/metabolism ; Chromatin Immunoprecipitation ; *DNA Breaks, Double-Stranded ; DNA-Binding Proteins/metabolism ; HEK293 Cells ; HeLa Cells ; Histone-Lysine N-Methyltransferase/chemistry/*metabolism ; Histones/*chemistry/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/*metabolism ; Lysine/*metabolism ; Methylation ; Nuclear Proteins/chemistry/metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Protein Transport ; Protein-Serine-Threonine Kinases/metabolism ; Repressor Proteins/chemistry/*metabolism ; Trans-Activators/chemistry/metabolism ; Tumor Suppressor Proteins/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2011-03-25
    Description: Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-kappaB signalling was indicated by mutations in 11 members of the NF-kappaB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560292/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560292/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapman, Michael A -- Lawrence, Michael S -- Keats, Jonathan J -- Cibulskis, Kristian -- Sougnez, Carrie -- Schinzel, Anna C -- Harview, Christina L -- Brunet, Jean-Philippe -- Ahmann, Gregory J -- Adli, Mazhar -- Anderson, Kenneth C -- Ardlie, Kristin G -- Auclair, Daniel -- Baker, Angela -- Bergsagel, P Leif -- Bernstein, Bradley E -- Drier, Yotam -- Fonseca, Rafael -- Gabriel, Stacey B -- Hofmeister, Craig C -- Jagannath, Sundar -- Jakubowiak, Andrzej J -- Krishnan, Amrita -- Levy, Joan -- Liefeld, Ted -- Lonial, Sagar -- Mahan, Scott -- Mfuko, Bunmi -- Monti, Stefano -- Perkins, Louise M -- Onofrio, Robb -- Pugh, Trevor J -- Rajkumar, S Vincent -- Ramos, Alex H -- Siegel, David S -- Sivachenko, Andrey -- Stewart, A Keith -- Trudel, Suzanne -- Vij, Ravi -- Voet, Douglas -- Winckler, Wendy -- Zimmerman, Todd -- Carpten, John -- Trent, Jeff -- Hahn, William C -- Garraway, Levi A -- Meyerson, Matthew -- Lander, Eric S -- Getz, Gad -- Golub, Todd R -- K12 CA133250/CA/NCI NIH HHS/ -- R01 AG020686/AG/NIA NIH HHS/ -- R01 AG020686-07/AG/NIA NIH HHS/ -- R01 CA133115/CA/NCI NIH HHS/ -- R01 CA133115-04/CA/NCI NIH HHS/ -- R01 CA133966/CA/NCI NIH HHS/ -- R01 CA133966-03/CA/NCI NIH HHS/ -- England -- Nature. 2011 Mar 24;471(7339):467-72. doi: 10.1038/nature09837.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02412, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21430775" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Blood Coagulation/genetics ; CpG Islands/genetics ; DNA Mutational Analysis ; DNA Repair/genetics ; Exons/genetics ; Exosome Multienzyme Ribonuclease Complex ; Genome, Human/*genetics ; Genomics ; Histones/metabolism ; Homeodomain Proteins/genetics ; Homeostasis/genetics ; Humans ; Methylation ; Models, Molecular ; Molecular Sequence Data ; Multiple Myeloma/drug therapy/enzymology/*genetics/metabolism ; Mutation/*genetics ; NF-kappa B/metabolism ; Oncogenes/genetics ; Open Reading Frames/genetics ; Protein Biosynthesis/genetics ; Protein Conformation ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors/genetics/metabolism ; RNA Processing, Post-Transcriptional/genetics ; Ribonucleases/chemistry/genetics ; Signal Transduction/genetics ; Transcription, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1569-8041
    Keywords: chromosomal translocations ; cyclin D1 ; FGFR3 ; MMSET ; multiple myeloma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Chromosome translocations involving the immunoglobulinheavy chain gene (IgH) on 14q32 are a seminal event in the pathogenesis ofmany B-cell malignancies. Since myeloma is a post-germinal center tumor ofmature, isotype switched plasma cells, we hypothesized that 14q32translocations would usually involve IgH switch regions. Materials and methods:We analyzed a panel of 21 human myelomacell lines using a Southern blot assay to detect illegitimate rearrangementsinvolving the switch regions. We then cloned the breakpoints, developed probesfor FISH analysis, and characterized the oncogenes dysregulated by thetranslocations. Results:Only half of the cell lines demonstrated a 14q32abnormality by conventional karyotypic analysis, but we were able to identifytranslocations involving IgH switch regions in 15 of 21 lines, including allof the lines in which a 14q32 translocations was notidentified byconventional karyotypic analysis. Six cell lines have an Ig translocationinvolving 11q13 with overexpression of cyclin D1. Six cell lines have an Igtranslocation involving 16q23 with overexpression of c-maf. Fivelines have an Ig translocations involving 4p16 with overexpression of FGFR3and a novel gene, MMSET. The 4p16 breakpoints occur within the 5′introns of MMSET, and are associated with IgH-MMSET hybrid mRNA transcripts.The remaining five cell lines have translocations involving other loci,including: 6p25 (MUM1), 8q24 (c-myc), and 21q22 (?AML1). Conclusions:Recurrent Ig translocations identify at least threedistinct molecular subtypes of myeloma. Our long-term goal is to determine ifthere are phenotypic, prognostic and therapeutic differences associated withthese molecular subtypes.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    facet.materialart.
    Unknown
    American Society of Hematology (ASH)
    In: Blood
    Publication Date: 2018-08-10
    Keywords: Free Research Articles
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...