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Masayuki Seki

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Mong Sing Lai; Masayuki Seki; Shusuke Tada; Takemi Enomoto
Rmi1 functions in S phase-mediated cohesion establishment via a pathway involving the Ctf18-RFC complex and Mrc1.
Hironoshin Nomura; Masayuki Seki; Syusuke Tada; Akira Yasui; Akari Yoshimura; Takato Edo; Shin-ichiro Kanno; Takemi Enomoto
WRNIP1 accumulates at laser light irradiated sites rapidly via its ubiquitin-binding zinc finger domain and independently from its ATPase domain.
Katsuyuki Ishikawa; Lena R. Kundu; Ryo Natsume; Naohito Nozaki; Tatsuya Ohsumi; Takemi Enomoto; Masami Horikoshi; Toshiya Senda; Shusuke Tada; Masayuki Seki
Roles of histone chaperone CIA/Asf1 in nascent DNA elongation during nucleosome replication.

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All Publications

2012: Mong Sing Lai; Masayuki Seki; Shusuke Tada; Takemi Enomoto
Rmi1 functions in S phase-mediated cohesion establishment via a pathway involving the Ctf18-RFC complex and Mrc1.
Biochemical and biophysical research communications 2012;427(3):682-6.
2012: Hironoshin Nomura; Masayuki Seki; Syusuke Tada; Akira Yasui; Akari Yoshimura; Takato Edo; Shin-ichiro Kanno; Takemi Enomoto
WRNIP1 accumulates at laser light irradiated sites rapidly via its ubiquitin-binding zinc finger domain and independently from its ATPase domain.
Biochemical and biophysical research communications 2012;417(4):1145-50.
2011: Katsuyuki Ishikawa; Lena R. Kundu; Ryo Natsume; Naohito Nozaki; Tatsuya Ohsumi; Takemi Enomoto; Masami Horikoshi; Toshiya Senda; Shusuke Tada; Masayuki Seki
Roles of histone chaperone CIA/Asf1 in nascent DNA elongation during nucleosome replication.
Genes to cells : devoted to molecular & cellular mechanisms 2011;16(10):1050-62.
2011: Satoshi Kawashima; Kazuko Matsubara; Yu Nakabayashi; Norihiko Sano; Masayuki Seki; Kozo Tanaka; Takemi Enomoto; Masami Horikoshi
Global analysis of core histones reveals nucleosomal surfaces required for chromosome bi-orientation.
The EMBO journal 2011;30(16):3353-67.
2011: Yoshifumi Hosono; Masamichi Ishiai; Takuya Abe; Takemi Enomoto; Minoru Takata; Masayuki Seki
The role of SNM1 family nucleases in etoposide-induced apoptosis.
Biochemical and biophysical research communications 2011;410(3):568-73.
2011: Lena R. Kundu; Masayuki Seki; Nanae Watanabe; Hiromu Murofushi; Asako Furukohri; Shou Waga; Alan J Score; J Julian Blow; Masami Horikoshi; Takemi Enomoto; Shusuke Tada
Biphasic chromatin binding of histone chaperone FACT during eukaryotic chromatin DNA replication.
Biochimica et biophysica acta 2011;1813(6):1129-36.
2011: Mayumi Ohkawa; Yoshiya Ohno; Kazue Masuko; Akiko Takeuchi; Kentaro Suda; Akihiro Kubo; Rieko Kawahara; Shogo Okazaki; Toshiyuki Tanaka; Hideyuki Saya; Masayuki Seki; Takemi Enomoto; Hideki Yagi; Yoshiyuki Hashimoto; T Masuko
Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy.
Biochemical and biophysical research communications 2011;406(4):649-55.
2011: Takuya Abe; Akari Yoshimura; Yoshifumi Hosono; Shusuke Tada; Masayuki Seki; Takemi Enomoto
The N-terminal region of RECQL4 lacking the helicase domain is both essential and sufficient for the viability of vertebrate cells. Role of the N-terminal region of RECQL4 in cells.
Biochimica et biophysica acta 2011;1813(3):473-9.
2010: Hirohito Endo; Satoshi Kawashima; Lui Sato; Mong Sing Lai; Takemi Enomoto; Masayuki Seki; Masami Horikoshi
Chromatin dynamics mediated by histone modifiers and histone chaperones in postreplicative recombination.
Genes to cells : devoted to molecular & cellular mechanisms 2010;15(9):945-58.
2010: Lena R. Kundu; Yuji Kumata; Naoko Kakusho; Saori Watanabe; Asako Furukohri; Shou Waga; Masayuki Seki; Hisao Masai; Takemi Enomoto; Shusuke Tada
Deregulated Cdc6 inhibits DNA replication and suppresses Cdc7-mediated phosphorylation of Mcm2-7 complex.
Nucleic acids research 2010;38(16):5409-18.
2010: Eri Inoue; Keizo Tano; Hanako Yoshii; Jun Nakamura; Shusuke Tada; Masami Watanabe; Masayuki Seki; Takemi Enomoto
SOD1 Is Essential for the Viability of DT40 Cells and Nuclear SOD1 Functions as a Guardian of Genomic DNA.
Journal of nucleic acids 2010;2010():.
2009: Takashi Ohuchi; Masayuki Seki; Kazuto Kugou; Shusuke Tada; Kunihiro Ohta; Takemi Enomoto
Accumulation of sumoylated Rad52 in checkpoint mutants perturbed in DNA replication.
DNA repair 2009;8(6):690-6.
2009: Akari Yoshimura; Masayuki Seki; Makoto Kanamori; Satoshi Tateishi; Toshiki Tsurimoto; Shusuke Tada; Takemi Enomoto
Physical and functional interaction between WRNIP1 and RAD18.
Genes & genetic systems 2009;84(2):171-8.
2009: Masayuki Seki; Mong Sing Lai; Takemi Enomoto
[Passing through cohesin ring by replication forks and establishment of sister chromatid cohesion: what's the connection?].
Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 2009;54(4 Suppl):543-6.
2009: Shunya Takada; Eri Inoue; Keizo Tano; Hanako Yoshii; Takuya Abe; Akari Yoshimura; Motomu Akita; Shusuke Tada; Masami Watanabe; Masayuki Seki; Takemi Enomoto
Generation and characterization of cells that can be conditionally depleted of mitochondrial SOD2.
Biochemical and biophysical research communications 2009;379(2):233-8.
2009: Takashi Tsuyama; Saori Watanabe; Ayako Aoki; Yunje Cho; Masayuki Seki; Takemi Enomoto; Shusuke Tada
Repression of nascent strand elongation by deregulated Cdt1 during DNA replication in Xenopus egg extracts.
Molecular biology of the cell 2009;20(3):937-47.
2008: Takuya Abe; Masamichi Ishiai; Yoshifumi Hosono; Akari Yoshimura; Shusuke Tada; Noritaka Adachi; Hideki Koyama; Minoru Takata; Shunichi Takeda; Takemi Enomoto; Masayuki Seki
KU70/80, DNA-PKcs, and Artemis are essential for the rapid induction of apoptosis after massive DSB formation.
Cellular signalling 2008;20(11):1978-85.
2008: Katsuaki Nishino; Eri Inoue; Shunya Takada; Takuya Abe; Motomu Akita; Akari Yoshimura; Shusuke Tada; Masahiko Kobayashi; Ken-Ichi Yamamoto; Masayuki Seki; Takemi Enomoto
A novel role for Rad17 in homologous recombination.
Genes & genetic systems 2008;83(5):427-31.
2008: Masayuki Seki; Makoto Otsuki; Yutaka Ishii; Shusuke Tada; Takemi Enomoto
RecQ family helicases in genome stability: lessons from gene disruption studies in DT40 cells.
Cell cycle (Georgetown, Tex.) 2008;7(16):2472-8.
2008: Takashi Ohuchi; Masayuki Seki; Takemi Enomoto
Nuclear localization of Rad52 is pre-requisite for its sumoylation.
Biochemical and biophysical research communications 2008;372(1):126-30.
2008: Takashi Ohuchi; Masayuki Seki; Dana Branzei; Daisuke Maeda; Ayako Ui; Hideaki Ogiwara; Shusuke Tada; Takemi Enomoto
Rad52 sumoylation and its involvement in the efficient induction of homologous recombination.
DNA repair 2008;7(6):879-89.
2008: Tomoko Hayashi; Masayuki Seki; Eri Inoue; Akari Yoshimura; Yumiko Kusa; Shusuke Tada; Takemi Enomoto
Vertebrate WRNIP1 and BLM are required for efficient maintenance of genome stability.
Genes & genetic systems 2008;83(1):95-100.
2008: Makoto Otsuki; Masayuki Seki; Eri Inoue; Takuya Abe; Yoshiyasu Narita; Akari Yoshimura; Shusuke Tada; Yutaka Ishii; Takemi Enomoto
Analyses of functional interaction between RECQL1, RECQL5, and BLM which physically interact with DNA topoisomerase IIIalpha.
Biochimica et biophysica acta 2008;1782(2):75-81.
2007: Makoto Otsuki; Masayuki Seki; Eri Inoue; Akari Yoshimura; Genta Kato; Saki Yamanouchi; Yoh-ichi Kawabe; Shusuke Tada; Akira Shinohara; Jun-ichiro Komura; Tetsuya Ono; Shunichi Takeda; Yutaka Ishii; Takemi Enomoto
Functional interactions between BLM and XRCC3 in the cell.
The Journal of cell biology 2007;179(1):53-63.
2007: Mong Sing Lai; Masayuki Seki; Ayako Ui; Takemi Enomoto
Rmi1, a member of the Sgs1-Top3 complex in budding yeast, contributes to sister chromatid cohesion.
EMBO reports 2007;8(7):685-90.
2007: Yu Peng Dong; Masayuki Seki; Akari Yoshimura; Eri Inoue; Shinya Furukawa; Shusuke Tada; Takemi Enomoto
WRN functions in a RAD18-dependent damage avoidance pathway.
Biological & pharmaceutical bulletin 2007;30(6):1080-3.
2007: Ayako Ui; Masayuki Seki; Hideaki Ogiwara; Mong Sing Lai; Kazuo Yamamoto; Shusuke Tada; Takemi Enomoto
Activation of a novel pathway involving Mms1 and Rad59 in sgs1 cells.
Biochemical and biophysical research communications 2007;356(4):1031-7.
2007: Hideaki Ogiwara; Takemi Enomoto; Masayuki Seki
The INO80 chromatin remodeling complex functions in sister chromatid cohesion.
Cell cycle (Georgetown, Tex.) 2007;6(9):1090-5.
2007: Satoshi Kawashima; Hideaki Ogiwara; Shusuke Tada; Masahiko Harata; Ulrike Wintersberger; Takemi Enomoto; Masayuki Seki
The INO80 complex is required for damage-induced recombination.
Biochemical and biophysical research communications 2007;355(3):835-41.
2007: Makoto Otsuki; Masayuki Seki; Yoh-ichi Kawabe; Eri Inoue; Yu Peng Dong; Takuya Abe; Genta Kato; Akari Yoshimura; Shusuke Tada; Takemi Enomoto
WRN counteracts the NHEJ pathway upon camptothecin exposure.
Biochemical and biophysical research communications 2007;355(2):477-82.
2007: Yuji Tomizawa; Ayako Ui; Fumitoshi Onoda; Hideaki Ogiwara; Shusuke Tada; Takemi Enomoto; Masayuki Seki
Rad50 is involved in MMS-induced recombination between homologous chromosomes in mitotic cells.
Genes & genetic systems 2007;82(2):157-60.
2007: Yuji Kumata; Shusuke Tada; Yumie Yamanada; Takashi Tsuyama; Takayuki Kobayashi; Yu Peng Dong; Kyoko Ikegami; Hiromu Murofushi; Masayuki Seki; Takemi Enomoto
Possible involvement of RecQL4 in the repair of double-strand DNA breaks in Xenopus egg extracts.
Biochimica et biophysica acta 2007;1773(4):556-64.
2007: Hideaki Ogiwara; Ayako Ui; Mong Sing Lai; Takemi Enomoto; Masayuki Seki
Chl1 and Ctf4 are required for damage-induced recombinations.
Biochemical and biophysical research communications 2007;354(1):222-6.
2007: Hideaki Ogiwara; Takashi Ohuchi; Ayako Ui; Shusuke Tada; Takemi Enomoto; Masayuki Seki
Ctf18 is required for homologous recombination-mediated double-strand break repair.
Nucleic acids research 2007;35(15):4989-5000.
2007: Hideaki Ogiwara; Ayako Ui; Satoshi Kawashima; Kazuto Kugou; Fumitoshi Onoda; Hitoshi Iwahashi; Masahiko Harata; Kunihiro Ohta; Takemi Enomoto; Masayuki Seki
Actin-related protein Arp4 functions in kinetochore assembly.
Nucleic acids research 2007;35(9):3109-17.
2007: Hideaki Ogiwara; Ayako Ui; Takemi Enomoto; Masayuki Seki
Role of Elg1 protein in double strand break repair.
Nucleic acids research 2007;35(2):353-62.
2006: Takashi Tsuyama; Katsutoshi Inou; Masayuki Seki; Takahiko Seki; Yuji Kumata; Takayuki Kobayashi; Keiji Kimura; Fumio Hanaoka; Takemi Enomoto; Shusuke Tada
Chromatin loading of Smc5/6 is induced by DNA replication but not by DNA double-strand breaks.
Biochemical and biophysical research communications 2006;351(4):935-9.
2006: Niloofar Davoodi Vijeh Motlagh; Masayuki Seki; Dana Branzei; Takemi Enomoto
Mgs1 and Rad18/Rad5/Mms2 are required for survival of Saccharomyces cerevisiae mutants with novel temperature/cold sensitive alleles of the DNA polymerase delta subunit, Pol31.
DNA repair 2006;5(12):1459-74.
2006: Akari Yoshimura; Katsuaki Nishino; Jun Takezawa; Shusuke Tada; Takayuki Kobayashi; Eiichiro Sonoda; Takuo Kawamoto; Shunichi Takeda; Yutaka Ishii; Kouichi Yamada; Takemi Enomoto; Masayuki Seki
A novel Rad18 function involved in protection of the vertebrate genome after exposure to camptothecin.
DNA repair 2006;5(11):1307-16.
2006: Dana Branzei; Julie Sollier; Giordano Liberi; Xiaolan Zhao; Daisuke Maeda; Masayuki Seki; Takemi Enomoto; Kunihiro Ohta; Marco Foiani
Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks.
Cell 2006;127(3):509-22.
2006: Akari Yoshimura; Masayuki Seki; Tomoko Hayashi; Yumiko Kusa; Shusuke Tada; Yutaka Ishii; Takemi Enomoto
Functional relationships between Rad18 and WRNIP1 in vertebrate cells.
Biological & pharmaceutical bulletin 2006;29(11):2192-6.
2006: parimal karmakar; Masayuki Seki; Makoto Kanamori; Kazunari Hashiguchi; Makoto Ohtsuki; Eriko Murata; Eri Inoue; Shusuke Tada; Li Lan; Akira Yasui; Takemi Enomoto
BLM is an early responder to DNA double-strand breaks.
Biochemical and biophysical research communications 2006;348(1):62-9.
2006: Masayuki Seki; Takayuki Nakagawa; Takahiko Seki; Genta Kato; Shusuke Tada; Yuriko Takahashi; Akari Yoshimura; Takayuki Kobayashi; Ayako Aoki; Makoto Otsuki; Felix A Habermann; Hideyuki Tanabe; Yutaka Ishii; Takemi Enomoto
Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids.
Molecular and cellular biology 2006;26(16):6299-307.
2006: Yoh-ichi Kawabe; Masayuki Seki; Akari Yoshimura; Katsuaki Nishino; Tomoko Hayashi; Takashi Takeuchi; Sota Iguchi; Yumiko Kusa; Makoto Ohtsuki; Takashi Tsuyama; Osamu Imamura; Takehisa Matsumoto; Yasuhiro Furuichi; Shusuke Tada; Takemi Enomoto
Analyses of the interaction of WRNIP1 with Werner syndrome protein (WRN) in vitro and in the cell.
DNA repair 2006;5(7):816-28.
2006: Shusuke Tada; Masayuki Seki; Takemi Enomoto
[DNA helicases and progeroid syndromes].
Seikagaku. The Journal of Japanese Biochemical Society 2006;78(3):221-9.
2006: Masayuki Seki; Shusuke Tada; Takemi Enomoto
Function of recQ family helicase in genome stability.
Sub-cellular biochemistry 2006;40():49-73.
2006: Hideaki Ogiwara; Ayako Ui; Fumitoshi Onoda; Shusuke Tada; Takemi Enomoto; Masayuki Seki
Dpb11, the budding yeast homolog of TopBP1, functions with the checkpoint clamp in recombination repair.
Nucleic acids research 2006;34(11):3389-98.
2005: Ayako Ui; Masayuki Seki; Hideaki Ogiwara; Ryoko Onodera; Shin-ichi Fukushige; Fumitoshi Onoda; Takemi Enomoto
The ability of Sgs1 to interact with DNA topoisomerase III is essential for damage-induced recombination.
DNA repair 2005;4(2):191-201.
2005: Takashi Tsuyama; Shusuke Tada; Saori Watanabe; Masayuki Seki; Takemi Enomoto
Licensing for DNA replication requires a strict sequential assembly of Cdc6 and Cdt1 onto chromatin in Xenopus egg extracts.
Nucleic acids research 2005;33(2):765-75.
2004: Dana Branzei; Masayuki Seki; Takemi Enomoto
Rad18/Rad5/Mms2-mediated polyubiquitination of PCNA is implicated in replication completion during replication stress.
Genes to cells : devoted to molecular & cellular mechanisms 2004;9(11):1031-42.
2004: Fumitoshi Onoda; Masayuki Seki; Wensheng Wang; Takemi Enomoto
The hyper unequal sister chromatid recombination in an sgs1 mutant of budding yeast requires MSH2.
DNA repair 2004;3(10):1355-62.
2004: Fumitoshi Onoda; Masahiro Takeda; Masayuki Seki; Daisuke Maeda; Jun-ichi Tajima; Ayako Ui; Hideki Yagi; Takemi Enomoto
SMC6 is required for MMS-induced interchromosomal and sister chromatid recombinations in Saccharomyces cerevisiae.
DNA repair 2004;3(4):429-39.
2004: Daisuke Maeda; Masayuki Seki; Fumitoshi Onoda; Dana Branzei; Yoh-ichi Kawabe; Takemi Enomoto
Ubc9 is required for damage-tolerance and damage-induced interchromosomal homologous recombination in S. cerevisiae.
DNA repair 2004;3(3):335-41.
2004: Wensheng Wang; Masayuki Seki; Makoto Otsuki; Shusuke Tada; Noriaki Takao; Ken-ichi Yamamoto; Makoto Hayashi; Masamitsu Honma; Takemi Enomoto
The absence of a functional relationship between ATM and BLM, the components of BASC, in DT40 cells.
Biochimica et biophysica acta 2004;1688(2):137-44.
2003: Wensheng Wang; Masayuki Seki; Yoshiyasu Narita; Takayuki Nakagawa; Akari Yoshimura; Makoto Otsuki; Yoh-ichi Kawabe; Shusuke Tada; Hideki Yagi; Yutaka Ishii; Takemi Enomoto
Functional relation among RecQ family helicases RecQL1, RecQL5, and BLM in cell growth and sister chromatid exchange formation.
Molecular and cellular biology 2003;23(10):3527-35.
2003: Nao Odagiri; Masayuki Seki; Fumitoshi Onoda; Akari Yoshimura; Sei Watanabe; Takemi Enomoto
Budding yeast mms4 is epistatic with rad52 and the function of Mms4 can be replaced by a bacterial Holliday junction resolvase.
DNA repair 2003;2(3):347-58.
2002: Dana Branzei; Masayuki Seki; Fumitoshi Onoda; Takemi Enomoto
The product of Saccharomyces cerevisiae WHIP/MGS1, a gene related to replication factor C genes, interacts functionally with DNA polymerase delta.
Molecular genetics and genomics : MGG 2002;268(3):371-86.
2002: Tomoko Hayashi; Masayuki Seki; Daisuke Maeda; Wensheng Wang; Yoh-ichi Kawabe; Takahiko Seki; Hisato Saitoh; Tatsuo Fukagawa; Hideki Yagi; Takemi Enomoto
Ubc9 is essential for viability of higher eukaryotic cells.
Experimental cell research 2002;280(2):212-21.
2002: Dana Branzei; Masayuki Seki; Fumitoshi Onoda; Hideki Yagi; Yoh-ichi Kawabe; Takemi Enomoto
Characterization of the slow-growth phenotype of S. cerevisiae Whip/Mgs1 Sgs1 double deletion mutants.
DNA repair 2002;1(8):671-82.
2002: Takayuki Kobayashi; Shusuke Tada; Takashi Tsuyama; Hiromu Murofushi; Masayuki Seki; Takemi Enomoto
Focus-formation of replication protein A, activation of checkpoint system and DNA repair synthesis induced by DNA double-strand breaks in Xenopus egg extract.
Journal of cell science 2002;115(Pt 15):3159-69.
2002: Ryoko Onodera; Masayuki Seki; Ayako Ui; Yurie Satoh; Atsuko Miyajima; Fumitoshi Onoda; Takemi Enomoto
Functional and physical interaction between Sgs1 and Top3 and Sgs1-independent function of Top3 in DNA recombination repair.
Genes & genetic systems 2002;77(1):11-21.
2001: Shusuke Tada; T Kobayashi; A Omori; Yumiko Kusa; N Okumura; H Kodaira; Yukio Ishimi; Masayuki Seki; Takemi Enomoto
Molecular cloning of a cDNA encoding mouse DNA helicase B, which has homology to Escherichia coli RecD protein, and identification of a mutation in the DNA helicase B from tsFT848 temperature-sensitive DNA replication mutant cells.
Nucleic acids research 2001;29(18):3835-40.
2001: Ayako Ui; Yurie Satoh; Fumitoshi Onoda; Atsuko Miyajima; Masayuki Seki; Takemi Enomoto
The N-terminal region of Sgs1, which interacts with Top3, is required for complementation of MMS sensitivity and suppression of hyper-recombination in sgs1 disruptants.
Molecular genetics and genomics : MGG 2001;265(5):837-50.
2001: Dana Branzei; Tomoko Hayashi; H Suzuki; T Masuko; Fumitoshi Onoda; SJ Heo; Hitoshi Ikeda; A Shimamoto; Yasuhiro Furuichi; Masayuki Seki; Takemi Enomoto
A novel protein interacts with the Werner's syndrome gene product physically and functionally.
The Journal of biological chemistry 2001;276(23):20364-9.
2001: Fumitoshi Onoda; Masayuki Seki; Atsuko Miyajima; Takemi Enomoto
Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae.
Molecular & general genetics : MGG 2001;264(5):702-8.
2000: Atsuko Miyajima; Masayuki Seki; Fumitoshi Onoda; Ayako Ui; Yurie Satoh; Y Ohno; Takemi Enomoto
Different domains of Sgs1 are required for mitotic and meiotic functions.
Genes & genetic systems 2000;75(6):319-26.
2000: Atsuko Miyajima; Masayuki Seki; Fumitoshi Onoda; M Shiratori; N Odagiri; K Ohta; Y Kikuchi; Y Ohno; Takemi Enomoto
Sgs1 helicase activity is required for mitotic but apparently not for meiotic functions.
Molecular and cellular biology 2000;20(17):6399-409.
2000: Yoh-ichi Kawabe; Masayuki Seki; Takahiko Seki; W S Wang; O Imamura; Yasuhiro Furuichi; H Saitoh; Takemi Enomoto
Covalent modification of the Werner's syndrome gene product with the ubiquitin-related protein, SUMO-1.
The Journal of biological chemistry 2000;275(28):20963-6.
2000: Wensheng Wang; Masayuki Seki; Y Narita; E Sonoda; Shunichi Takeda; K Yamada; T Masuko; T Katada; Takemi Enomoto
Possible association of BLM in decreasing DNA double strand breaks during DNA replication.
The EMBO journal 2000;19(13):3428-35.
2000: Fumitoshi Onoda; Masayuki Seki; Atsuko Miyajima; Takemi Enomoto
Elevation of sister chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom's syndrome gene.
Mutation research 2000;459(3):203-9.