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  • 1
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    Human exonuclease 1 connects nucleotide excision repair (NER) processing with checkpoint activation in response to UV irradiation [Genetics] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-08-18
    Description: UV light induces DNA lesions, which are removed by nucleotide excision repair (NER). Exonuclease 1 (EXO1) is highly conserved from yeast to human and is implicated in numerous DNA metabolic pathways, including repair, recombination, replication, and telomere maintenance. Here we show that hEXO1 is involved in the cellular response to UV irradiation in human cells. After local UV irradiation, fluorescent-tagged hEXO1 localizes, together with NER factors, at the sites of damage in nonreplicating cells. hEXO1 accumulation requires XPF-dependent processing of UV-induced lesions and is enhanced by inhibition of DNA repair synthesis. In nonreplicating cells, depletion of hEXO1 reduces unscheduled DNA synthesis after UV irradiation, prevents ubiquitylation of histone H2A, and impairs activation of the checkpoint signal transduction cascade in response to UV damage. These findings reveal a key role for hEXO1 in the UV-induced DNA damage response linking NER to checkpoint activation in human cells.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-12-17
    Description: Translesion synthesis (TLS) is the major pathway by which mammalian cells replicate across DNA lesions. Upon DNA damage, ubiquitination of proliferating cell nuclear antigen (PCNA) induces bypass of the lesion by directing the replication machinery into the TLS pathway. Yet, how this modification is recognized and interpreted in the cell remains unclear. Here we describe the identification of two ubiquitin (Ub)-binding domains (UBM and UBZ), which are evolutionarily conserved in all Y-family TLS polymerases (pols). These domains are required for binding of poleta and poliota to ubiquitin, their accumulation in replication factories, and their interaction with monoubiquitinated PCNA. Moreover, the UBZ domain of poleta is essential to efficiently restore a normal response to ultraviolet irradiation in xeroderma pigmentosum variant (XP-V) fibroblasts. Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bienko, Marzena -- Green, Catherine M -- Crosetto, Nicola -- Rudolf, Fabian -- Zapart, Grzegorz -- Coull, Barry -- Kannouche, Patricia -- Wider, Gerhard -- Peter, Matthias -- Lehmann, Alan R -- Hofmann, Kay -- Dikic, Ivan -- New York, N.Y. -- Science. 2005 Dec 16;310(5755):1821-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biochemistry II, Goethe University Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16357261" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Cell Line ; Computational Biology ; DNA/*biosynthesis ; *DNA Damage ; DNA Repair ; DNA Replication ; DNA-Directed DNA Polymerase/*chemistry/genetics/*metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Nuclear Magnetic Resonance, Biomolecular ; Point Mutation ; Proliferating Cell Nuclear Antigen/metabolism ; Protein Binding ; Protein Conformation ; Protein Interaction Mapping ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/metabolism ; Transfection ; Ubiquitin/*metabolism ; Xeroderma Pigmentosum/genetics ; Zinc Fingers
    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)
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  • 3
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    Structure and mechanism of human DNA polymerase eta (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-06-26
    Description: The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Poleta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Poleta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Poleta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Poleta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Poleta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Poleta in replicating through D loop and DNA fragile sites.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2899710/" 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/PMC2899710/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biertumpfel, Christian -- Zhao, Ye -- Kondo, Yuji -- Ramon-Maiques, Santiago -- Gregory, Mark -- Lee, Jae Young -- Masutani, Chikahide -- Lehmann, Alan R -- Hanaoka, Fumio -- Yang, Wei -- G0501450/Medical Research Council/United Kingdom -- Z01 DK036146-01/Intramural NIH HHS/ -- ZIA DK036146-03/Intramural NIH HHS/ -- ZIA DK036146-04/Intramural NIH HHS/ -- ZIA DK036146-05/Intramural NIH HHS/ -- England -- Nature. 2010 Jun 24;465(7301):1044-8. doi: 10.1038/nature09196.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, NIDDK, NIH, 9000 Rockville Pike, Building 5, Room B103, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20577208" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/analogs & derivatives/metabolism ; Base Sequence ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; DNA Damage ; DNA-Directed DNA Polymerase/*chemistry/genetics/*metabolism ; Humans ; Kinetics ; Models, Molecular ; Mutation, Missense/genetics ; Pyrimidine Dimers/genetics/metabolism ; Structure-Activity Relationship ; Xeroderma Pigmentosum/enzymology/genetics
    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)
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  • 4
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    Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-09-02
    Description: The radiosensitive mutant xrs-6, derived from Chinese hamster ovary cells, is defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. The human XRCC5 DNA repair gene, which complements this mutant, is shown here through genetic and biochemical evidence to be the 80-kilodalton subunit of the Ku protein. Ku binds to free double-stranded DNA ends and is the DNA-binding component of the DNA-dependent protein kinase. Thus, the Ku protein is involved in DNA repair and in V(D)J recombination, and these results may also indicate a role for the Ku-DNA-dependent protein kinase complex in those same processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taccioli, G E -- Gottlieb, T M -- Blunt, T -- Priestley, A -- Demengeot, J -- Mizuta, R -- Lehmann, A R -- Alt, F W -- Jackson, S P -- Jeggo, P A -- AI 20047/AI/NIAID NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1994 Sep 2;265(5177):1442-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Children's Hospital, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8073286" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigens, Nuclear ; Base Sequence ; CHO Cells ; Cell Survival/radiation effects ; Cloning, Molecular ; Cricetinae ; DNA Damage ; *DNA Helicases ; DNA Repair/*genetics ; DNA-Binding Proteins/*genetics/metabolism ; *Genes, Immunoglobulin ; Genetic Complementation Test ; Humans ; Hybrid Cells ; Molecular Sequence Data ; Nuclear Proteins/*genetics/metabolism ; Receptors, Antigen, T-Cell/*genetics ; *Recombination, Genetic ; Transfection
    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)
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  • 5
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    A Platinum-Copper Nugget Rich In Calcite: Evidence For Hydrothermal Pt3Cu (2017)
    Mineralogical Association of Canada
    Details
    Publication Date: 2017-02-03
    Description: An alluvial grain, 1.5 mm in length, occurs in the holotype material, a heavy-mineral concentrate, of the minerals kitagohaite, Pt 7 Cu, and luberoite, Pt 5 Se 4, from the Lubero region, North Kivu, Democratic Republic of the Congo. The grain is remarkable due to abundant inclusions of gangue within a metallic matrix. Here, the grain is characterized by electron-microprobe analysis as consisting of two Pt–Cu intermetallic compounds with calcite inclusions. The grain has a metallic core with Pt:Cu atomic ratios between 2.1 and 2.3. The core is enveloped by a Pt–Cu rim with Pt:Cu atomic ratios close to unity, corresponding to the mineral hongshiite (PtCu). The core composition is within the compositional field of synthetic Pt 3 Cu formed below about 600 °C in the Pt–Cu system. The calcite inclusions have MnO/FeO 〉 1, which is interpreted to reflect oxidizing conditions within the stability field of hematite. The low proportion of iron is compatible with the absence of iron in the Pt 3 Cu core and in the hongshiite rim. Hematite does occur as inclusions in other Pt–Cu nuggets of the heavy-mineral concentrate. The importance of the calcite-rich Pt–Cu nugget is that it indicates a calcite-lode setting, where the nugget is likely to have originated from a calcite-saturated hydrothermal brine.
    Print ISSN: 0008-4476
    Topics: Geosciences
    Published by Mineralogical Association of Canada
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  • 6
    Electronic Resource
    Electronic Resource
    Artefact in the Measurement of the Molecular Weight of Pulse Labelled DNA (1969)
    [s.l.] : Nature Publishing Group
    Nature 221 (1969), S. 1053-1056 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] We have obtained exactly the same results with a murine lymphoma cell (L5178Y) grown in tissue culture, and have shown that there is no need to invoke any special intermediate which is involved in DNA replication in order to explain the experimental results. The peak molecular weight of pulse ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/2211053b0
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  • 7
    Electronic Resource
    Electronic Resource
    Human Disorders Showing Increased Sensitivity to the Induction of Genetic Damage (1978)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 12 (1978), S. 95-115 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ge.12.120178.000523
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  • 8
    Electronic Resource
    Electronic Resource
    30 S DNA: intermediate or artefact? (1974)
    [s.l.] : Nature Publishing Group
    Nature 247 (1974), S. 243-243 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] SIR,-Goldstein and Rutman1 have pulse-labelled the DNA of Ehrlich ascites cells growing intraperitoneally in a mouse with either 3H or 14C-thymidine. The DNA was subsequently extracted from the cells and its molecular weight measured on gradients of alkaline sucrose. After short pulse times (〈2 ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/247243a0
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  • 9
    Electronic Resource
    Electronic Resource
    Biological effects of ultraviolet radiation (1979)
    [s.l.] : Nature Publishing Group
    Nature 278 (1979), S. 484-484 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] IT has long been known that sunlight has both beneficial and deleterious effects on man. Many of these effects are caused by the ultraviolet region of the solar spectrum, which has somewhat rabitrarily been divided into three sections-UV-C (wavelength 200-290 nm), UV-B (290-320 nm) and UV-A ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/278484a0
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  • 10
    Electronic Resource
    Electronic Resource
    Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity (1975)
    [s.l.] : Nature Publishing Group
    Nature 258 (1975), S. 427-429 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1 y-Ray response of cultured human fibroblasts. Linesfitted by eye. 0,1BR, normal, age 25 yr, male, 7 experknents^o'o& 2BI, nor-mal, 25'yr, male, 8 experiments; Q, BCNSlBIf 38 yr, male, 5 experiments; double triangles, BCNS2BI, 74 yr, female, 4 ex-periments; o, BCNS3B1, 14 yr, male, 5 ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/258427a0
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