FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2023579322> ?p ?o ?g. }

• W2023579322 endingPage "1550" @default.
• W2023579322 startingPage "1541" @default.
• W2023579322 abstract "DNA-dependent protein kinase (DNA-PK) is involved in joining DNA double-strand breaks induced by ionizing radiation or V(D)J recombination. The kinase is activated by DNA ends and composed of a DNA binding subunit, Ku, and a catalytic subunit, DNA-PKCS. To define the DNA structure required for kinase activation, we synthesized a series of DNA molecules and tested their interactions with purified DNA-PKCS. The addition of unpaired single strands to blunt DNA ends increased binding and activation of the kinase. When single-stranded loops were added to the DNA ends, binding was preserved, but kinase activation was severely reduced. Obstruction of DNA ends by streptavidin reduced both binding and activation of the kinase. Significantly, short single-stranded oligonucleotides of 3–10 bases were capable of activating DNA-PKCS. Taken together, these data indicate that kinase activation involves a specific interaction with free single-stranded DNA ends. The structure of DNA-PKCS contains an open channel large enough for double-stranded DNA and an adjacent enclosed cavity with the dimensions of single-stranded DNA. The data presented here support a model in which duplex DNA binds to the open channel, and a single-stranded DNA end is inserted into the enclosed cavity to activate the kinase. DNA-dependent protein kinase (DNA-PK) is involved in joining DNA double-strand breaks induced by ionizing radiation or V(D)J recombination. The kinase is activated by DNA ends and composed of a DNA binding subunit, Ku, and a catalytic subunit, DNA-PKCS. To define the DNA structure required for kinase activation, we synthesized a series of DNA molecules and tested their interactions with purified DNA-PKCS. The addition of unpaired single strands to blunt DNA ends increased binding and activation of the kinase. When single-stranded loops were added to the DNA ends, binding was preserved, but kinase activation was severely reduced. Obstruction of DNA ends by streptavidin reduced both binding and activation of the kinase. Significantly, short single-stranded oligonucleotides of 3–10 bases were capable of activating DNA-PKCS. Taken together, these data indicate that kinase activation involves a specific interaction with free single-stranded DNA ends. The structure of DNA-PKCS contains an open channel large enough for double-stranded DNA and an adjacent enclosed cavity with the dimensions of single-stranded DNA. The data presented here support a model in which duplex DNA binds to the open channel, and a single-stranded DNA end is inserted into the enclosed cavity to activate the kinase. double-strand break base pair(s) DNA-dependent protein kinase catalytic subunit of DNA-PK electrophoretic mobility shift assay single-stranded loop Cells recognize and respond to a multitude of different DNA lesions by activating pathways for apoptosis, cell cycle arrest, or DNA repair. Little is known about how DNA lesions are recognized and transduced into a signal for these cellular responses. In the case of DNA double-strand breaks (DSBs)1 induced by ionizing radiation, recognition is critically important, because DSBs can lead to chromosomal fragmentation and cell death, or to chromosomal translocations and cancer.Ionizing radiation activates the c-Abl tyrosine kinase, which has undefined physiological functions (1.Kharbanda S. Ren R. Pandey P. Shafman T. Feller S. Weichselbaum R. Kufe D. Nature. 1995; 376: 785-788Crossref PubMed Scopus (456) Google Scholar, 2.Liu Z.-G. Baskaran R. Lea-Chou E.L. Wood L.D. Chen Y. Karin M. Wang J.Y.J. Nature. 1996; 384: 273-276Crossref PubMed Scopus (346) Google Scholar). Ionizing radiation also activates the ATM kinase and DNA-dependent protein kinase (DNA-PK), which have homologous kinase domains. ATM phosphorylates p53 to induce cell cycle arrest or apoptosis (3.Giaccia A.J. Kastan M.B. Genes Dev. 1998; 12: 2973-2983Crossref PubMed Scopus (1170) Google Scholar). DNA-PK is required for the repair of DSBs produced by ionizing radiation and V(D)J recombination, the process that generates immunological diversity in antibodies and T cell receptors (4.Smider V. Chu G. Semin. Immunol. 1997; 9: 189-197Crossref PubMed Scopus (53) Google Scholar). Understanding how DNA-PK is activated by DSBs can establish a paradigm for how proteins signal the presence of DNA lesions.DNA-PK is a serine-threonine protein kinase consisting of DNA binding and catalytic subunits. The DNA binding subunit is the Ku protein, a heterodimer of 70 and 86 kDa that binds to DNA ends, nicks, and structures containing a transition fork between double-stranded DNA and two single strands (5.Mimori T. Hardin J.A. J. Biol. Chem. 1986; 261: 10375-10379Abstract Full Text PDF PubMed Google Scholar, 6.Falzon M. Fewell J.W. Kuff E.L. J. Biol. Chem. 1993; 268: 10546-10552Abstract Full Text PDF PubMed Google Scholar, 7.Paillard S. Strauss F. Nucleic Acids Res. 1991; 19: 5619-5624Crossref PubMed Scopus (188) Google Scholar, 8.de Vries E. van Driel W. Bergsma W.G. Arnberg A.C. van der Vliet P.C. J. Mol. Biol. 1989; 208: 65-78Crossref PubMed Scopus (216) Google Scholar, 9.Blier P. Griffith A. Craft J. Hardin J. J. Biol. Chem. 1993; 268: 7594-7601Abstract Full Text PDF PubMed Google Scholar). The catalytic subunit of DNA-PK (DNA-PKCS) is a 465-kDa polypeptide (10.Hartley K.O. Gell D. Smith G.C.M. Zhang H. Divecha N. Connelly M.A. Admon A. Lees-Miller S.P. Anderson C.W. Jackson S.P. Cell. 1995; 82: 849-856Abstract Full Text PDF PubMed Scopus (669) Google Scholar) that is sufficient for the kinase activity of the enzyme (11.Yaneva M. Kowalewski T. Lieber M. EMBO J. 1997; 16: 5098-5112Crossref PubMed Scopus (267) Google Scholar, 12.Hammarsten O. Chu G. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 525-530Crossref PubMed Scopus (200) Google Scholar, 13.West R. Yaneva M. Lieber M. Mol. Cell. Biol. 1998; 18: 5908-5920Crossref PubMed Scopus (142) Google Scholar). DNA-PKCS is recruited for activation at DNA ends by Ku at physiological salt concentrations (14.Gottlieb T.M. Jackson S.P. Cell. 1993; 72: 131-142Abstract Full Text PDF PubMed Scopus (1019) Google Scholar, 15.Suwa A. Hirakata M. Takeda Y. Jesch S. Mimori S. Hardin J. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 6904-6908Crossref PubMed Scopus (168) Google Scholar), but the kinase is fully activated by DNA ends in the absence of Ku at low salt concentrations (12.Hammarsten O. Chu G. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 525-530Crossref PubMed Scopus (200) Google Scholar).Several lines of evidence indicate that DNA-PK is involved in the cellular response to DSBs. The otherwise latent kinase activity of DNA-PK is activated by DNA ends (14.Gottlieb T.M. Jackson S.P. Cell. 1993; 72: 131-142Abstract Full Text PDF PubMed Scopus (1019) Google Scholar, 16.Carter T. Vancurova I. Sun I. Lou W. DeLeon S. Mol. Cell. Biol. 1990; 10: 6460-6471Crossref PubMed Scopus (245) Google Scholar). The catalytic domain of DNA-PKCS is mutated in the severe combined immunodeficiency mouse (17.Blunt T. Gell D. Fox M. Taccioli G.E. Lehman A.R. Jackson S.P. Jeggo P.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 10285-10290Crossref PubMed Scopus (303) Google Scholar, 18.Danska J.S. Holland D.P. Mariathasan S. Williams K.M. Guidos C.J. Mol. Cell. Biol. 1996; 16: 5507-5517Crossref PubMed Scopus (178) Google Scholar), which is defective in the repair of DSBs (19.Hendrickson E. Qin X.Q. Bump E. Schatz D. Oettinger M. Weaver D. Proc. Natl. Acad. Sci. U. S. A. 1991; 88: 4061-4065Crossref PubMed Scopus (283) Google Scholar, 20.Fulop G.M. Phillips R.A. Nature. 1990; 347: 479-482Crossref PubMed Scopus (436) Google Scholar, 21.Biedermann K.A. Sun J.R. Giaccia A.J. Tosto L.M. Brown J.M. Proc. Natl. Acad. Sci. U. S. A. 1991; 88: 1394-1397Crossref PubMed Scopus (450) Google Scholar). Additional studies have suggested that the catalytic kinase activity of DNA-PK is required for rejoining DSBs both in intact cells (22.Kurimasa A. Kumano S. Boubnov N. Story M. Tung C.S. Peterson S. Chen D. Mol. Cell. Biol. 1999; 19: 3877-3884Crossref PubMed Scopus (255) Google Scholar) and in a cell free system (23.Baumann P. West S.C. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 14066-14070Crossref PubMed Scopus (273) Google Scholar).A number of DNA structures have been tested for their ability to activate DNA-PK. DNA with blunt ends, 5′ overhanging ends, or 3′ overhanging ends activate DNA-PK with equal efficiency (14.Gottlieb T.M. Jackson S.P. Cell. 1993; 72: 131-142Abstract Full Text PDF PubMed Scopus (1019) Google Scholar), whereas double-stranded DNA with hairpin ends fails to activate the kinase (24.Smider V. Rathmell W.K. Brown G. Lewis S. Chu G. Mol. Cell. Biol. 1998; 18: 6853-6858Crossref PubMed Google Scholar). Supercoiled plasmid DNA fails to activate DNA-PK, but supercoiled plasmid DNA containing the NRE1 sequence from mouse mammary tumor virus was reported to activate the kinase (25.Giffin W. Torrance H. Rodda D. Prefontaine G. Pope L. Hache R. Nature. 1996; 380: 265-268Crossref PubMed Scopus (197) Google Scholar, 26.Giffin W. Kwast-Welfeld J. Rodda D.J. Prefontaine G.G. Traykova-Andonova M. Zhang Y. Weigel N.L. Lefebvre Y.A. Hache R.J. J. Biol. Chem. 1997; 272: 5647-5658Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar). Based on these studies, it was not clear what specific DNA structure was critical for the activation of DNA-PK.In these earlier studies, the DNA structures were tested with different enzyme preparations and a variety of protein substrates. Interpretations of the results were potentially confounded by several factors: DNA preparations may have contained contaminating DNA structures, and enzyme preparations often included Ku, which may have altered or obscured properties of the DNA structures upon binding. Therefore, to define precisely the DNA structure required for kinase activation, we undertook a systematic study of a homogeneous preparation of DNA-PKCS with a series of gel-purified DNA structures in the absence of any cofactors or contaminating proteins. Cells recognize and respond to a multitude of different DNA lesions by activating pathways for apoptosis, cell cycle arrest, or DNA repair. Little is known about how DNA lesions are recognized and transduced into a signal for these cellular responses. In the case of DNA double-strand breaks (DSBs)1 induced by ionizing radiation, recognition is critically important, because DSBs can lead to chromosomal fragmentation and cell death, or to chromosomal translocations and cancer. Ionizing radiation activates the c-Abl tyrosine kinase, which has undefined physiological functions (1.Kharbanda S. Ren R. Pandey P. Shafman T. Feller S. Weichselbaum R. Kufe D. Nature. 1995; 376: 785-788Crossref PubMed Scopus (456) Google Scholar, 2.Liu Z.-G. Baskaran R. Lea-Chou E.L. Wood L.D. Chen Y. Karin M. Wang J.Y.J. Nature. 1996; 384: 273-276Crossref PubMed Scopus (346) Google Scholar). Ionizing radiation also activates the ATM kinase and DNA-dependent protein kinase (DNA-PK), which have homologous kinase domains. ATM phosphorylates p53 to induce cell cycle arrest or apoptosis (3.Giaccia A.J. Kastan M.B. Genes Dev. 1998; 12: 2973-2983Crossref PubMed Scopus (1170) Google Scholar). DNA-PK is required for the repair of DSBs produced by ionizing radiation and V(D)J recombination, the process that generates immunological diversity in antibodies and T cell receptors (4.Smider V. Chu G. Semin. Immunol. 1997; 9: 189-197Crossref PubMed Scopus (53) Google Scholar). Understanding how DNA-PK is activated by DSBs can establish a paradigm for how proteins signal the presence of DNA lesions. DNA-PK is a serine-threonine protein kinase consisting of DNA binding and catalytic subunits. The DNA binding subunit is the Ku protein, a heterodimer of 70 and 86 kDa that binds to DNA ends, nicks, and structures containing a transition fork between double-stranded DNA and two single strands (5.Mimori T. Hardin J.A. J. Biol. Chem. 1986; 261: 10375-10379Abstract Full Text PDF PubMed Google Scholar, 6.Falzon M. Fewell J.W. Kuff E.L. J. Biol. Chem. 1993; 268: 10546-10552Abstract Full Text PDF PubMed Google Scholar, 7.Paillard S. Strauss F. Nucleic Acids Res. 1991; 19: 5619-5624Crossref PubMed Scopus (188) Google Scholar, 8.de Vries E. van Driel W. Bergsma W.G. Arnberg A.C. van der Vliet P.C. J. Mol. Biol. 1989; 208: 65-78Crossref PubMed Scopus (216) Google Scholar, 9.Blier P. Griffith A. Craft J. Hardin J. J. Biol. Chem. 1993; 268: 7594-7601Abstract Full Text PDF PubMed Google Scholar). The catalytic subunit of DNA-PK (DNA-PKCS) is a 465-kDa polypeptide (10.Hartley K.O. Gell D. Smith G.C.M. Zhang H. Divecha N. Connelly M.A. Admon A. Lees-Miller S.P. Anderson C.W. Jackson S.P. Cell. 1995; 82: 849-856Abstract Full Text PDF PubMed Scopus (669) Google Scholar) that is sufficient for the kinase activity of the enzyme (11.Yaneva M. Kowalewski T. Lieber M. EMBO J. 1997; 16: 5098-5112Crossref PubMed Scopus (267) Google Scholar, 12.Hammarsten O. Chu G. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 525-530Crossref PubMed Scopus (200) Google Scholar, 13.West R. Yaneva M. Lieber M. Mol. Cell. Biol. 1998; 18: 5908-5920Crossref PubMed Scopus (142) Google Scholar). DNA-PKCS is recruited for activation at DNA ends by Ku at physiological salt concentrations (14.Gottlieb T.M. Jackson S.P. Cell. 1993; 72: 131-142Abstract Full Text PDF PubMed Scopus (1019) Google Scholar, 15.Suwa A. Hirakata M. Takeda Y. Jesch S. Mimori S. Hardin J. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 6904-6908Crossref PubMed Scopus (168) Google Scholar), but the kinase is fully activated by DNA ends in the absence of Ku at low salt concentrations (12.Hammarsten O. Chu G. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 525-530Crossref PubMed Scopus (200) Google Scholar). Several lines of evidence indicate that DNA-PK is involved in the cellular response to DSBs. The otherwise latent kinase activity of DNA-PK is activated by DNA ends (14.Gottlieb T.M. Jackson S.P. Cell. 1993; 72: 131-142Abstract Full Text PDF PubMed Scopus (1019) Google Scholar, 16.Carter T. Vancurova I. Sun I. Lou W. DeLeon S. Mol. Cell. Biol. 1990; 10: 6460-6471Crossref PubMed Scopus (245) Google Scholar). The catalytic domain of DNA-PKCS is mutated in the severe combined immunodeficiency mouse (17.Blunt T. Gell D. Fox M. Taccioli G.E. Lehman A.R. Jackson S.P. Jeggo P.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 10285-10290Crossref PubMed Scopus (303) Google Scholar, 18.Danska J.S. Holland D.P. Mariathasan S. Williams K.M. Guidos C.J. Mol. Cell. Biol. 1996; 16: 5507-5517Crossref PubMed Scopus (178) Google Scholar), which is defective in the repair of DSBs (19.Hendrickson E. Qin X.Q. Bump E. Schatz D. Oettinger M. Weaver D. Proc. Natl. Acad. Sci. U. S. A. 1991; 88: 4061-4065Crossref PubMed Scopus (283) Google Scholar, 20.Fulop G.M. Phillips R.A. Nature. 1990; 347: 479-482Crossref PubMed Scopus (436) Google Scholar, 21.Biedermann K.A. Sun J.R. Giaccia A.J. Tosto L.M. Brown J.M. Proc. Natl. Acad. Sci. U. S. A. 1991; 88: 1394-1397Crossref PubMed Scopus (450) Google Scholar). Additional studies have suggested that the catalytic kinase activity of DNA-PK is required for rejoining DSBs both in intact cells (22.Kurimasa A. Kumano S. Boubnov N. Story M. Tung C.S. Peterson S. Chen D. Mol. Cell. Biol. 1999; 19: 3877-3884Crossref PubMed Scopus (255) Google Scholar) and in a cell free system (23.Baumann P. West S.C. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 14066-14070Crossref PubMed Scopus (273) Google Scholar). A number of DNA structures have been tested for their ability to activate DNA-PK. DNA with blunt ends, 5′ overhanging ends, or 3′ overhanging ends activate DNA-PK with equal efficiency (14.Gottlieb T.M. Jackson S.P. Cell. 1993; 72: 131-142Abstract Full Text PDF PubMed Scopus (1019) Google Scholar), whereas double-stranded DNA with hairpin ends fails to activate the kinase (24.Smider V. Rathmell W.K. Brown G. Lewis S. Chu G. Mol. Cell. Biol. 1998; 18: 6853-6858Crossref PubMed Google Scholar). Supercoiled plasmid DNA fails to activate DNA-PK, but supercoiled plasmid DNA containing the NRE1 sequence from mouse mammary tumor virus was reported to activate the kinase (25.Giffin W. Torrance H. Rodda D. Prefontaine G. Pope L. Hache R. Nature. 1996; 380: 265-268Crossref PubMed Scopus (197) Google Scholar, 26.Giffin W. Kwast-Welfeld J. Rodda D.J. Prefontaine G.G. Traykova-Andonova M. Zhang Y. Weigel N.L. Lefebvre Y.A. Hache R.J. J. Biol. Chem. 1997; 272: 5647-5658Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar). Based on these studies, it was not clear what specific DNA structure was critical for the activation of DNA-PK. In these earlier studies, the DNA structures were tested with different enzyme preparations and a variety of protein substrates. Interpretations of the results were potentially confounded by several factors: DNA preparations may have contained contaminating DNA structures, and enzyme preparations often included Ku, which may have altered or obscured properties of the DNA structures upon binding. Therefore, to define precisely the DNA structure required for kinase activation, we undertook a systematic study of a homogeneous preparation of DNA-PKCS with a series of gel-purified DNA structures in the absence of any cofactors or contaminating proteins. We thank Dan Herschlag, Suzanne Admiraal, Vaughn Smider, Pehr Harbury, and David Halpin for advice." @default.
• W2023579322 created "2016-06-24" @default.
• W2023579322 creator A5002643791 @default.
• W2023579322 creator A5005971897 @default.
• W2023579322 creator A5043236428 @default.
• W2023579322 date "2000-01-01" @default.
• W2023579322 modified "2023-10-11" @default.
• W2023579322 title "Activation of DNA-dependent Protein Kinase by Single-stranded DNA Ends" @default.
• W2023579322 cites W1509547277 @default.
• W2023579322 cites W1516845708 @default.
• W2023579322 cites W1532833901 @default.
• W2023579322 cites W1550569484 @default.
• W2023579322 cites W1557970645 @default.
• W2023579322 cites W1970232857 @default.
• W2023579322 cites W1974010399 @default.
• W2023579322 cites W1976897618 @default.
• W2023579322 cites W1977145510 @default.
• W2023579322 cites W1979303367 @default.
• W2023579322 cites W1981255217 @default.
• W2023579322 cites W1995796643 @default.
• W2023579322 cites W1997056099 @default.
• W2023579322 cites W2003196136 @default.
• W2023579322 cites W2004822307 @default.
• W2023579322 cites W2007635472 @default.
• W2023579322 cites W2010901031 @default.
• W2023579322 cites W2011320725 @default.
• W2023579322 cites W2023324317 @default.
• W2023579322 cites W2024877615 @default.
• W2023579322 cites W2033270381 @default.
• W2023579322 cites W2037517612 @default.
• W2023579322 cites W2038875604 @default.
• W2023579322 cites W2042645510 @default.
• W2023579322 cites W2053926251 @default.
• W2023579322 cites W2060527795 @default.
• W2023579322 cites W2072917278 @default.
• W2023579322 cites W2076023322 @default.
• W2023579322 cites W2079472423 @default.
• W2023579322 cites W2082910780 @default.
• W2023579322 cites W2094491029 @default.
• W2023579322 cites W2121550851 @default.
• W2023579322 cites W2144512576 @default.
• W2023579322 cites W2156299289 @default.
• W2023579322 cites W2159907784 @default.
• W2023579322 cites W2163658254 @default.
• W2023579322 cites W2165579893 @default.
• W2023579322 doi "https://doi.org/10.1074/jbc.275.3.1541" @default.
• W2023579322 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10636842" @default.
• W2023579322 hasPublicationYear "2000" @default.
• W2023579322 type Work @default.
• W2023579322 sameAs 2023579322 @default.
• W2023579322 citedByCount "103" @default.
• W2023579322 countsByYear W20235793222012 @default.
• W2023579322 countsByYear W20235793222013 @default.
• W2023579322 countsByYear W20235793222014 @default.
• W2023579322 countsByYear W20235793222015 @default.
• W2023579322 countsByYear W20235793222016 @default.
• W2023579322 countsByYear W20235793222017 @default.
• W2023579322 countsByYear W20235793222018 @default.
• W2023579322 countsByYear W20235793222020 @default.
• W2023579322 countsByYear W20235793222021 @default.
• W2023579322 countsByYear W20235793222022 @default.
• W2023579322 countsByYear W20235793222023 @default.
• W2023579322 crossrefType "journal-article" @default.
• W2023579322 hasAuthorship W2023579322A5002643791 @default.
• W2023579322 hasAuthorship W2023579322A5005971897 @default.
• W2023579322 hasAuthorship W2023579322A5043236428 @default.
• W2023579322 hasBestOaLocation W20235793221 @default.
• W2023579322 hasConcept C12554922 @default.
• W2023579322 hasConcept C143425029 @default.
• W2023579322 hasConcept C153911025 @default.
• W2023579322 hasConcept C184235292 @default.
• W2023579322 hasConcept C185592680 @default.
• W2023579322 hasConcept C54355233 @default.
• W2023579322 hasConcept C552990157 @default.
• W2023579322 hasConcept C55493867 @default.
• W2023579322 hasConcept C68748289 @default.
• W2023579322 hasConcept C86803240 @default.
• W2023579322 hasConcept C95444343 @default.
• W2023579322 hasConcept C97029542 @default.
• W2023579322 hasConceptScore W2023579322C12554922 @default.
• W2023579322 hasConceptScore W2023579322C143425029 @default.
• W2023579322 hasConceptScore W2023579322C153911025 @default.
• W2023579322 hasConceptScore W2023579322C184235292 @default.
• W2023579322 hasConceptScore W2023579322C185592680 @default.
• W2023579322 hasConceptScore W2023579322C54355233 @default.
• W2023579322 hasConceptScore W2023579322C552990157 @default.
• W2023579322 hasConceptScore W2023579322C55493867 @default.
• W2023579322 hasConceptScore W2023579322C68748289 @default.
• W2023579322 hasConceptScore W2023579322C86803240 @default.
• W2023579322 hasConceptScore W2023579322C95444343 @default.
• W2023579322 hasConceptScore W2023579322C97029542 @default.
• W2023579322 hasIssue "3" @default.
• W2023579322 hasLocation W20235793221 @default.
• W2023579322 hasOpenAccess W2023579322 @default.
• W2023579322 hasPrimaryLocation W20235793221 @default.
• W2023579322 hasRelatedWork W1975990189 @default.
• W2023579322 hasRelatedWork W1983626749 @default.
• W2023579322 hasRelatedWork W2007214310 @default.

• next