Genomes and Genes
Summary: Immunologically detectable substances found in the CELL NUCLEUS.
- Almeida González D, Cabrera de León A, Rodríguez Pérez M, Brito Díaz B, González Hernández A, García García D, et al. Efficiency of different strategies to detect autoantibodies to extractable nuclear antigens. J Immunol Methods. 2010;360:89-95 pubmed publisherAutoantibodies to extractable nuclear antigens (anti-ENA) are identified mainly in samples positive for antinuclear antibodies (ANA)...
- Jiang C, Deshmukh U, Gaskin F, Bagavant H, Hanson J, David C, et al. Differential responses to Smith D autoantigen by mice with HLA-DR and HLA-DQ transgenes: dominant responses by HLA-DR3 transgenic mice with diversification of autoantibodies to small nuclear ribonucleoprotein, double-stranded DNA, and nuclear antigen. J Immunol. 2010;184:1085-91 pubmed publisher..In addition, our findings provide insights into the origin of the anti-dsDNA Abs often detected in patients with systemic lupus erythematosus. ..
- Guirouilh Barbat J, Rass E, Plo I, Bertrand P, Lopez B. Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends. Proc Natl Acad Sci U S A. 2007;104:20902-7 pubmed..More specifically, these data showed that the KU80/XRCC4 pathway is conservative and not intrinsically error-prone but can accommodate non-fully complementary ends at the cost of limited mutagenesis. ..
- He F, Li L, Kim D, Wen B, Deng X, Gutin P, et al. Adenovirus-mediated expression of a dominant negative Ku70 fragment radiosensitizes human tumor cells under aerobic and hypoxic conditions. Cancer Res. 2007;67:634-42 pubmed..If radiation-resistant tumor cells could be sensitized by down-regulating the cellular level/activity of Ku/DNA-PK, this approach could be evaluated as an adjuvant to radiation therapy. ..
- Schulte Uentrop L, El Awady R, Schliecker L, Willers H, Dahm Daphi J. Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks. Nucleic Acids Res. 2008;36:2561-9 pubmed publisher..Thus, I-SceI-induced breaks may resemble DSBs arising during normal DNA metabolism and mouse development. The removal of these breaks likely has different genetic requirements than the repair of radiation-induced DSBs. ..
- Fattah K, Ruis B, Hendrickson E. Mutations to Ku reveal differences in human somatic cell lines. DNA Repair (Amst). 2008;7:762-74 pubmed publisher..Collectively, these studies demonstrate the importance of proper biallelic expression of these genes for NHEJ and telomere maintenance and they provide insights into why these genes are uniquely essential for primates. ..
- Rampakakis E, Di Paola D, Zannis Hadjopoulos M. Ku is involved in cell growth, DNA replication and G1-S transition. J Cell Sci. 2008;121:590-600 pubmed publisher..The data suggest the interplay between the DNA-replication and cell-cycle machineries and shed light on a new role of Ku in G1-S transition. ..
- Krauss S, Spence J, Bahmanyar S, Barth A, Go M, Czerwinski D, et al. Downregulation of protein 4.1R, a mature centriole protein, disrupts centrosomes, alters cell cycle progression, and perturbs mitotic spindles and anaphase. Mol Cell Biol. 2008;28:2283-94 pubmed publisher..1R makes crucial contributions to the structural integrity of centrosomes and mitotic spindles which normally enable mitosis and anaphase to proceed with the coordinated precision required to avoid pathological events. ..
- Rivera Calzada A, Spagnolo L, Pearl L, Llorca O. Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs. EMBO Rep. 2007;8:56-62 pubmed
- Li H, Choi Y, Hanes M, Marple T, Vogel H, Hasty P. Deleting Ku70 is milder than deleting Ku80 in p53-mutant mice and cells. Oncogene. 2009;28:1875-8 pubmed publisher..Thus, Ku80 may function outside the Ku heterodimer to influence DNA damage repair presenting the possibility that Ku80 influenced the open coding ends in a manner that suppressed a cancer-causing translocation. ..
- Jiang D, Zhou Y, Moxley R, Jarrett H. Purification and identification of positive regulators binding to a novel element in the c-Jun promoter. Biochemistry. 2008;47:9318-34 pubmed publisher..Similarly, Ku70 wild type transfection can also upregulate c-jun promoter activity. Thus, Ku80-c-jun activates c-jun expression by binding to this GAGCCTC element in the c-jun promoter and Ku70 may also serve a role. ..
- Roberts S, Ramsden D. Loading of the nonhomologous end joining factor, Ku, on protein-occluded DNA ends. J Biol Chem. 2007;282:10605-13 pubmed..We suggest a model where Ku utilizes an unusual characteristic of its three-dimensional structure to recognize certain protein-occluded ends without the extensive remodeling of chromatin structure required by other DNA repair pathways. ..
- Iijima K, Muranaka C, Kobayashi J, Sakamoto S, Komatsu K, Matsuura S, et al. NBS1 regulates a novel apoptotic pathway through Bax activation. DNA Repair (Amst). 2008;7:1705-16 pubmed publisher..Thus, NBS1 is a key protein involved in the prevention of carcinogenesis, not only through the precise repair of damaged DNA by homologous recombination (HR) but also by its role in the elimination of inappropriately repaired cells. ..
- Oya Y, Watanabe N, Owada T, Oki M, Hirose K, Suto A, et al. Development of autoimmune hepatitis-like disease and production of autoantibodies to nuclear antigens in mice lacking B and T lymphocyte attenuator. Arthritis Rheum. 2008;58:2498-510 pubmed publisher..We examined the levels of immunoglobulins and autoantibodies to nuclear antigens and the activation status of T cells in BTLA(-/-) mice...
- Mansour W, Schumacher S, Rosskopf R, Rhein T, Schmidt Petersen F, Gatzemeier F, et al. Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks. Nucleic Acids Res. 2008;36:4088-98 pubmed publisher..Furthermore, the cellular choice of repair pathways is reversible and can be influenced at the level of effector proteins such as Ku80 or Rad51. ..
- Weinstock D, Brunet E, Jasin M. Formation of NHEJ-derived reciprocal chromosomal translocations does not require Ku70. Nat Cell Biol. 2007;9:978-81 pubmed..Surprisingly, translocations are increased in cells deficient for the nonhomologous end-joining (NHEJ) protein Ku70, implicating non-canonical joining pathways in their etiology. ..
- Gomez J, Gama V, Yoshida T, Sun W, Hayes P, Leskov K, et al. Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides. Biochem Soc Trans. 2007;35:797-801 pubmed..CPP5s have very low toxicity in vitro and in vivo and so may be useful tools in order to develop non-toxic drug-delivery technologies. ..
- Soutoglou E, Dorn J, Sengupta K, Jasin M, Nussenzweig A, Ried T, et al. Positional stability of single double-strand breaks in mammalian cells. Nat Cell Biol. 2007;9:675-82 pubmed..These results support a contact-first model in which chromosome translocations predominantly form among spatially proximal DSBs. ..
- Ilina E, Lavrik O, Khodyreva S. Ku antigen interacts with abasic sites. Biochim Biophys Acta. 2008;1784:1777-85 pubmed publisher..Ku antigen as a part of DNA-PK was shown to inhibit AP site cleavage by apurinic/apyrimidinic endonuclease 1. ..
- Kanno S, Kuzuoka H, Sasao S, Hong Z, Lan L, Nakajima S, et al. A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses. EMBO J. 2007;26:2094-103 pubmed..Various treatments that produce double-strand breaks induce formation of PALF foci, which fully coincide with gammaH2AX foci. Thus, PALF and the CYR motif may play important roles in DNA repair of higher eukaryotes. ..
- Bruce A, Bakke A, Gravett C, DeMaster L, Bielefeldt Ohmann H, Burnside K, et al. The ORF59 DNA polymerase processivity factor homologs of Old World primate RV2 rhadinoviruses are highly conserved nuclear antigens expressed in differentiated epithelium in infected macaques. Virol J. 2009;6:205 pubmed publisher..These studies will aid in the characterization of virus activation from latency to the replicative state, an important step for understanding the biology and transmission of rhadinoviruses, such as KSHV. ..
- Tomimatsu N, Tahimic C, Otsuki A, Burma S, Fukuhara A, Sato K, et al. Ku70/80 modulates ATM and ATR signaling pathways in response to DNA double strand breaks. J Biol Chem. 2007;282:10138-45 pubmed
- Bennardo N, Cheng A, Huang N, Stark J. Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair. PLoS Genet. 2008;4:e1000110 pubmed publisher..However, at later steps of repair, alt-NHEJ is a mechanistically distinct pathway of DSB repair, and thus may play a unique role in mutagenesis during cancer development and therapy...
- Ribes Zamora A, Mihalek I, Lichtarge O, Bertuch A. Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions. Nat Struct Mol Biol. 2007;14:301-7 pubmed..We propose a 'two-face' model for Ku and that divergent evolution of these faces allowed Ku's dual role in NHEJ and telomere maintenance. ..
- Li H, Vogel H, Holcomb V, Gu Y, Hasty P. Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer. Mol Cell Biol. 2007;27:8205-14 pubmed..Thus, our observations suggest that the Ku heterodimer is important for longevity assurance in mice since divergent genetic backgrounds and/or environments likely account for these previously reported differences...
- Li Y, Yokota T, Gama V, Yoshida T, Gomez J, Ishikawa K, et al. Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Cell Death Differ. 2007;14:2058-67 pubmed..These results indicate that Bax and Ku70 acetylation play important roles in Q79C-induced cell death, and that BIP may be useful in the development of therapeutics for polyQ diseases. ..
- Holcomb V, Vogel H, Hasty P. Deletion of Ku80 causes early aging independent of chronic inflammation and Rag-1-induced DSBs. Mech Ageing Dev. 2007;128:601-8 pubmed..Therefore, this study supports defective repair of spontaneous DNA damage as the root cause of early aging in Ku80-mutant mice. ..
- Costantini S, Woodbine L, Andreoli L, Jeggo P, Vindigni A. Interaction of the Ku heterodimer with the DNA ligase IV/Xrcc4 complex and its regulation by DNA-PK. DNA Repair (Amst). 2007;6:712-22 pubmed..Here, we show that DNA-PK kinase activity also results in disassembly of the Ku/DNA ligase IV/Xrcc4 complex. Collectively, our findings provide novel information on the protein-protein interactions that regulate NHEJ in cells. ..
- Grote J, König S, Ackermann D, Sopalla C, Benedyk M, Los M, et al. Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression. BMC Mol Biol. 2006;7:48 pubmed..The latter may indicate a possible link between S100 and inflammation-associated cancer. ..
- Yano K, Morotomi Yano K, Wang S, Uematsu N, Lee K, Asaithamby A, et al. Ku recruits XLF to DNA double-strand breaks. EMBO Rep. 2008;9:91-6 pubmed..Our observations showed the direct involvement of XLF in the dynamic assembly of the NHEJ machinery and provide mechanistic insights into DSB recognition. ..
- Cui X, Meek K. Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway. Proc Natl Acad Sci U S A. 2007;104:17046-51 pubmed..Here we demonstrate that non-RAG-mediated DSBs can be similarly forced into the NHEJ pathway by physical association with the RAG endonuclease. ..
- Saberi A, Hochegger H, Szuts D, Lan L, Yasui A, Sale J, et al. RAD18 and poly(ADP-ribose) polymerase independently suppress the access of nonhomologous end joining to double-strand breaks and facilitate homologous recombination-mediated repair. Mol Cell Biol. 2007;27:2562-71 pubmed..In conclusion, higher-eukaryotic cells separately employ PARP1 and Rad18 to suppress the toxic effects of NHEJ during the HR reaction at stalled replication forks. ..
- Uematsu N, Weterings E, Yano K, Morotomi Yano K, Jakob B, Taucher Scholz G, et al. Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks. J Cell Biol. 2007;177:219-29 pubmed..We suggest a model in which DNA-PK(CS) phosphorylation/autophosphorylation facilitates NHEJ by destabilizing the interaction of DNA-PK(CS) with the DNA ends. ..
- Shi L, Qiu D, Zhao G, Corthesy B, Lees Miller S, Reeves W, et al. Dynamic binding of Ku80, Ku70 and NF90 to the IL-2 promoter in vivo in activated T-cells. Nucleic Acids Res. 2007;35:2302-10 pubmed..Dynamic changes in binding of Ku80, Ku70 and NF90 to the IL-2 proximal promoter in vivo correlate with chromatin remodeling and transcriptional initiation in activated T-cells. ..
- Lebrun P, Montminy M, Van Obberghen E. Regulation of the pancreatic duodenal homeobox-1 protein by DNA-dependent protein kinase. J Biol Chem. 2005;280:38203-10 pubmed..e. glut2 and glucokinase. Our study demonstrates that radiation, through the activation of DNA-PK, may regulate PDX-1 protein expression. ..
- Howlett N, Scuric Z, D Andrea A, Schiestl R. Impaired DNA double strand break repair in cells from Nijmegen breakage syndrome patients. DNA Repair (Amst). 2006;5:251-7 pubmed
- Iwabuchi K, Hashimoto M, Matsui T, Kurihara T, Shimizu H, Adachi N, et al. 53BP1 contributes to survival of cells irradiated with X-ray during G1 without Ku70 or Artemis. Genes Cells. 2006;11:935-48 pubmed..These results demonstrate that the 53BP1-dependent repair pathway is important for survival of cells irradiated with IR during the G1 phase of the cell cycle. ..
- Dmitrieva N, Celeste A, Nussenzweig A, Burg M. Ku86 preserves chromatin integrity in cells adapted to high NaCl. Proc Natl Acad Sci U S A. 2005;102:10730-5 pubmed..We propose that Ku86 ameliorates the effects of high NaCl-induced DNA breaks in adapted cells by supporting alignment of the broken ends of the DNA and thus maintaining integrity of the fragmented chromatin. ..
- Bossuyt X, Luyckx A. Antibodies to extractable nuclear antigens in antinuclear antibody-negative samples. Clin Chem. 2005;51:2426-7 pubmed
- Di Virgilio M, Gautier J. Repair of double-strand breaks by nonhomologous end joining in the absence of Mre11. J Cell Biol. 2005;171:765-71 pubmed..Finally, Ku70-independent end-joining events are not affected by Mre11 loss. Our data demonstrate that the MRN complex is not required for efficient and accurate NHEJ-mediated repair of DSBs in this vertebrate system. ..
- Gullo C, Au M, Feng G, Teoh G. The biology of Ku and its potential oncogenic role in cancer. Biochim Biophys Acta. 2006;1765:223-34 pubmed..These studies may also increase our understanding of how Ku autoantibodies are generated in autoimmune diseases. ..
- Jovanovic M, Dynan W. Terminal DNA structure and ATP influence binding parameters of the DNA-dependent protein kinase at an early step prior to DNA synapsis. Nucleic Acids Res. 2006;34:1112-20 pubmed..ATP and a nonhydrolyzable ATP analog also influence the stability of the DNA-PKcs*DNA complex, apparently by an allosteric mechanism that does not require DNA-PKcs autophosphorylation. ..
- Hochegger H, Dejsuphong D, Fukushima T, Morrison C, Sonoda E, Schreiber V, et al. Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells. EMBO J. 2006;25:1305-14 pubmed..Moreover, we found deletion of Ligase IV, another NHEJ gene, suppressed the camptothecin of PARP-1(-/-) cells. Our results suggest a new critical function for Parp in minimizing the suppressive effects of Ku and the NHEJ pathway on HR. ..
- Lomberk G, Bensi D, Fernandez Zapico M, Urrutia R. Evidence for the existence of an HP1-mediated subcode within the histone code. Nat Cell Biol. 2006;8:407-15 pubmed
- Spagnolo L, Rivera Calzada A, Pearl L, Llorca O. Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA DSB repair. Mol Cell. 2006;22:511-9 pubmed
- Wysocka J, Swigut T, Xiao H, Milne T, Kwon S, Landry J, et al. A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature. 2006;442:86-90 pubmed..We also identify a previously unknown function for the PHD finger as a highly specialized methyl-lysine-binding domain. ..
- Li H, Ilin S, Wang W, Duncan E, Wysocka J, Allis C, et al. Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF. Nature. 2006;442:91-5 pubmed..Our findings call attention to the PHD finger as a previously uncharacterized chromatin-binding module found in a large number of chromatin-associated proteins. ..
- Becker P. Gene regulation: a finger on the mark. Nature. 2006;442:31-2 pubmed
- Wang M, Wu W, Wu W, Rosidi B, Zhang L, Wang H, et al. PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res. 2006;34:6170-82 pubmed..This form of DSB repair is sensitive to PARP-1 inhibitors. The results define the function of PARP-1 in DSB repair and characterize a candidate pathway responsible for joining errors causing genomic instability and cancer. ..
- Bertolini L, Bertolini M, Anderson G, Maga E, Madden K, Murray J. Transient depletion of Ku70 and Xrcc4 by RNAi as a means to manipulate the non-homologous end-joining pathway. J Biotechnol. 2007;128:246-57 pubmed..The results highlight the possibility of a successful means to manipulate the NHEJ pathway by RNAi. ..
- Mari P, Florea B, Persengiev S, Verkaik N, Bruggenwirth H, Modesti M, et al. Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4. Proc Natl Acad Sci U S A. 2006;103:18597-602 pubmed..Our results suggest that this assembly constitutes the core of the NHEJ reaction and that XRCC4 may serve as a flexible tether between Ku70/80 and ligase IV. ..
- Kim J, Krasieva T, Kurumizaka H, Chen D, Taylor A, Yokomori K. Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells. J Cell Biol. 2005;170:341-7 pubmed..Damage site retention of NHEJ factors is transient, whereas HR factors persist at unrepaired lesions, revealing unique roles of the two pathways in mammalian cells. ..