ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-06-14
    Description: 53BP1 (also called TP53BP1) is a chromatin-associated factor that promotes immunoglobulin class switching and DNA double-strand-break (DSB) repair by non-homologous end joining. To accomplish its function in DNA repair, 53BP1 accumulates at DSB sites downstream of the RNF168 ubiquitin ligase. How ubiquitin recruits 53BP1 to break sites remains unknown as its relocalization involves recognition of histone H4 Lys 20 (H4K20) methylation by its Tudor domain. Here we elucidate how vertebrate 53BP1 is recruited to the chromatin that flanks DSB sites. We show that 53BP1 recognizes mononucleosomes containing dimethylated H4K20 (H4K20me2) and H2A ubiquitinated on Lys 15 (H2AK15ub), the latter being a product of RNF168 action on chromatin. 53BP1 binds to nucleosomes minimally as a dimer using its previously characterized methyl-lysine-binding Tudor domain and a carboxy-terminal extension, termed the ubiquitination-dependent recruitment (UDR) motif, which interacts with the epitope formed by H2AK15ub and its surrounding residues on the H2A tail. 53BP1 is therefore a bivalent histone modification reader that recognizes a histone 'code' produced by DSB signalling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955401/" 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/PMC3955401/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fradet-Turcotte, Amelie -- Canny, Marella D -- Escribano-Diaz, Cristina -- Orthwein, Alexandre -- Leung, Charles C Y -- Huang, Hao -- Landry, Marie-Claude -- Kitevski-LeBlanc, Julianne -- Noordermeer, Sylvie M -- Sicheri, Frank -- Durocher, Daniel -- 84297-1/Canadian Institutes of Health Research/Canada -- 84297-2/Canadian Institutes of Health Research/Canada -- MOP84297/Canadian Institutes of Health Research/Canada -- England -- Nature. 2013 Jul 4;499(7456):50-4. doi: 10.1038/nature12318. Epub 2013 Jun 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23760478" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Cell Cycle Proteins/chemistry/metabolism ; Cell Line ; Chromosomal Proteins, Non-Histone/chemistry/deficiency/genetics ; DNA Breaks, Double-Stranded ; *DNA Damage ; DNA-Binding Proteins/chemistry/deficiency/genetics ; Female ; Histones/*chemistry/*metabolism ; Humans ; Intracellular Signaling Peptides and ; Proteins/chemistry/deficiency/genetics/*metabolism ; Lysine/*metabolism ; Male ; Mice ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Nuclear Proteins/chemistry/metabolism ; Nucleosomes/chemistry/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Schizosaccharomyces ; Schizosaccharomyces pombe Proteins/chemistry/metabolism ; Signal Transduction ; Ubiquitin/*metabolism ; *Ubiquitination
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Mitosis inhibits DNA double-strand break repair to guard against telomere fusions (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-22
    Description: Mitotic cells inactivate DNA double-strand break (DSB) repair, but the rationale behind this suppression remains unknown. Here, we unravel how mitosis blocks DSB repair and determine the consequences of repair reactivation. Mitotic kinases phosphorylate the E3 ubiquitin ligase RNF8 and the nonhomologous end joining factor 53BP1 to inhibit their recruitment to DSB-flanking chromatin. Restoration of RNF8 and 53BP1 accumulation at mitotic DSB sites activates DNA repair but is, paradoxically, deleterious. Aberrantly controlled mitotic DSB repair leads to Aurora B kinase-dependent sister telomere fusions that produce dicentric chromosomes and aneuploidy, especially in the presence of exogenous genotoxic stress. We conclude that the capacity of mitotic DSB repair to destabilize the genome explains the necessity for its suppression during mitosis, principally due to the fusogenic potential of mitotic telomeres.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Orthwein, Alexandre -- Fradet-Turcotte, Amelie -- Noordermeer, Sylvie M -- Canny, Marella D -- Brun, Catherine M -- Strecker, Jonathan -- Escribano-Diaz, Cristina -- Durocher, Daniel -- MOP89754/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):189-93. doi: 10.1126/science.1248024. Epub 2014 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24652939" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aurora Kinase B/metabolism ; Cell Line, Tumor ; *DNA Breaks, Double-Stranded ; DNA End-Joining Repair/*physiology ; DNA-Binding Proteins/genetics/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; Mitosis/*physiology ; Nuclear Proteins/genetics/metabolism ; RNA, Small Interfering/genetics ; Telomere/genetics/*physiology ; Telomere Homeostasis/genetics/*physiology ; Trans-Activators/genetics/metabolism ; Ubiquitin-Protein Ligases/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5' end resection (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-03-25
    Description: Appropriate repair of DNA lesions and the inhibition of DNA repair activities at telomeres are crucial to prevent genomic instability. By fuelling the generation of genetic alterations and by compromising cell viability, genomic instability is a driving force in cancer and ageing. Here we identify MAD2L2 (also known as MAD2B or REV7) through functional genetic screening as a novel factor controlling DNA repair activities at mammalian telomeres. We show that MAD2L2 accumulates at uncapped telomeres and promotes non-homologous end-joining (NHEJ)-mediated fusion of deprotected chromosome ends and genomic instability. MAD2L2 depletion causes elongated 3' telomeric overhangs, indicating that MAD2L2 inhibits 5' end resection. End resection blocks NHEJ while committing to homology-directed repair, and is under the control of 53BP1, RIF1 and PTIP. Consistent with MAD2L2 promoting NHEJ-mediated telomere fusion by inhibiting 5' end resection, knockdown of the nucleases CTIP or EXO1 partially restores telomere-driven genomic instability in MAD2L2-depleted cells. Control of DNA repair by MAD2L2 is not limited to telomeres. MAD2L2 also accumulates and inhibits end resection at irradiation-induced DNA double-strand breaks and promotes end-joining of DNA double-strand breaks in several settings, including during immunoglobulin class switch recombination. These activities of MAD2L2 depend on ATM kinase activity, RNF8, RNF168, 53BP1 and RIF1, but not on PTIP, REV1 and REV3, the latter two acting with MAD2L2 in translesion synthesis. Together, our data establish MAD2L2 as a crucial contributor to the control of DNA repair activity by 53BP1 that promotes NHEJ by inhibiting 5' end resection downstream of RIF1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481296/" 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/PMC4481296/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boersma, Vera -- Moatti, Nathalie -- Segura-Bayona, Sandra -- Peuscher, Marieke H -- van der Torre, Jaco -- Wevers, Brigitte A -- Orthwein, Alexandre -- Durocher, Daniel -- Jacobs, Jacqueline J L -- 311565/European Research Council/International -- MOP89754/Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 May 28;521(7553):537-40. doi: 10.1038/nature14216. Epub 2015 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. ; The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. ; 1] The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada [2] Department of Molecular Genetics, University of Toronto, Ontario M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25799990" target="_blank"〉PubMed〈/a〉
    Keywords: Ataxia Telangiectasia Mutated Proteins/metabolism ; Carrier Proteins/metabolism ; Cell Line, Tumor ; *DNA Breaks, Double-Stranded/radiation effects ; *DNA End-Joining Repair/genetics ; DNA Repair Enzymes/metabolism ; DNA Replication ; DNA-Binding Proteins/metabolism ; Exodeoxyribonucleases/metabolism ; Genomic Instability ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Mad2 Proteins/*metabolism ; Nuclear Proteins/metabolism ; *Recombinational DNA Repair/genetics ; Telomere/genetics/*metabolism ; Telomere-Binding Proteins/metabolism ; Ubiquitin-Protein Ligases/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    A mechanism for the suppression of homologous recombination in G1 cells (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-12-10
    Description: DNA repair by homologous recombination is highly suppressed in G1 cells to ensure that mitotic recombination occurs solely between sister chromatids. Although many homologous recombination factors are cell-cycle regulated, the identity of the events that are both necessary and sufficient to suppress recombination in G1 cells is unknown. Here we report that the cell cycle controls the interaction of BRCA1 with PALB2-BRCA2 to constrain BRCA2 function to the S/G2 phases in human cells. We found that the BRCA1-interaction site on PALB2 is targeted by an E3 ubiquitin ligase composed of KEAP1, a PALB2-interacting protein, in complex with cullin-3 (CUL3)-RBX1 (ref. 6). PALB2 ubiquitylation suppresses its interaction with BRCA1 and is counteracted by the deubiquitylase USP11, which is itself under cell cycle control. Restoration of the BRCA1-PALB2 interaction combined with the activation of DNA-end resection is sufficient to induce homologous recombination in G1, as measured by RAD51 recruitment, unscheduled DNA synthesis and a CRISPR-Cas9-based gene-targeting assay. We conclude that the mechanism prohibiting homologous recombination in G1 minimally consists of the suppression of DNA-end resection coupled with a multi-step block of the recruitment of BRCA2 to DNA damage sites that involves the inhibition of BRCA1-PALB2-BRCA2 complex assembly. We speculate that the ability to induce homologous recombination in G1 cells with defined factors could spur the development of gene-targeting applications in non-dividing cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Orthwein, Alexandre -- Noordermeer, Sylvie M -- Wilson, Marcus D -- Landry, Sebastien -- Enchev, Radoslav I -- Sherker, Alana -- Munro, Meagan -- Pinder, Jordan -- Salsman, Jayme -- Dellaire, Graham -- Xia, Bing -- Peter, Matthias -- Durocher, Daniel -- FDN143343/Canadian Institutes of Health Research/Canada -- MOP84260/Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 Dec 17;528(7582):422-6. doi: 10.1038/nature16142. Epub 2015 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. ; ETH Zurich, Institute of Biochemistry, Department of Biology, Otto-Stern-Weg 3, CH-8093 Zurich, Switzerland. ; Department of Molecular Genetics, University of Toronto, Ontario M5S 3E1, Canada. ; Departments of Pathology and Biochemistry &Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada. ; Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26649820" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; BRCA1 Protein/metabolism ; BRCA2 Protein/metabolism ; CRISPR-Cas Systems/genetics ; Carrier Proteins/metabolism ; Cell Line ; Cullin Proteins/metabolism ; DNA/metabolism ; DNA Damage ; DNA Repair ; *G1 Phase ; G2 Phase ; Gene Targeting ; *Homologous Recombination ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Molecular Sequence Data ; Multiprotein Complexes/chemistry/metabolism ; Nuclear Proteins/chemistry/metabolism ; Protein Binding ; Rad51 Recombinase/metabolism ; S Phase ; Thiolester Hydrolases/metabolism ; Tumor Suppressor Proteins/chemistry/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    CTCF facilitates DNA double-strand break repair by enhancing homologous recombination repair (2017)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2017-05-25
    Description: The repair of DNA double-strand breaks (DSBs) is mediated via two major pathways, nonhomologous end joining (NHEJ) and homologous recombination (HR) repair. DSB repair is vital for cell survival, genome stability, and tumor suppression. In contrast to NHEJ, HR relies on extensive homology and templated DNA synthesis to restore the sequence surrounding the break site. We report a new role for the multifunctional protein CCCTC-binding factor (CTCF) in facilitating HR-mediated DSB repair. CTCF is recruited to DSB through its zinc finger domain independently of poly(ADP-ribose) polymers, known as PARylation, catalyzed by poly(ADP-ribose) polymerase 1 (PARP-1). CTCF ensures proper DSB repair kinetics in response to -irradiation, and the loss of CTCF compromises HR-mediated repair. Consistent with its role in HR, loss of CTCF results in hypersensitivity to DNA damage, inducing agents and inhibitors of PARP. Mechanistically, CTCF acts downstream of BRCA1 in the HR pathway and associates with BRCA2 in a PARylation-dependent manner, enhancing BRCA2 recruitment to DSB. In contrast, CTCF does not influence the recruitment of the NHEJ protein 53BP1 or LIGIV to DSB. Together, our findings establish for the first time that CTCF is an important regulator of the HR pathway.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...