2007 Fiscal Year Final Research Report Summary
Effect of repeat instability on cancer and neurological diseases
| Project/Area Number |
18590290
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
SUZUKI Motoshi Nagoya University, Graduate School of Medicine, Associate Professor (80236017)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Tohru Nagoya University, Graduate School of Medicine, Associate Professor (90402560)
MURATE Takashi Nagoya University, School of Medicine, Professor (30239537)
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| Project Period (FY) |
2006 – 2007
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| Keywords | genomic instability / DNA replication / HNPCC / neurological diseases / repeat instability |
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| Research Abstract |
In eulcaryotic cells, DNA polymerase a(pol a)initiates DNA synthesis at replication origins and at the 5'-ends of Okazaki fragments. Pol a lacks proofreading activity for correcting nucleotide misincorporation errors, but it extends mismatched 31-termini inefficiently. This can lead to premature termination of mismatched/misaligned DNA primers. The mutator polymerase L868F pol a catalyzes nucleotide misincorporation and misextension more frequently than wild type pol a. We have shown misaligned primers, but not the mismatched primers, generated by pol a can be extended by pol C in a reaction that requires PCNA. A yeast strain carrying L868F or L868M allele of pol a generated +1 frameshifts at a high rate, and this rate was decreased in strains lacking the catalytic subunit of pol C. Mutations were dependent on PCNA Lys164, and were downstream of the RAD18. Furthermore, inactivation of pol S exonuclease increased the proportion of pol t -dependent +1 frameshifts. These data suggest that PCNA and pol t cooperate in a replication error promoting pathway that may be targeted to misalignment errors. In this context, pol a PCNA-, and pol C -dependent DNA synthesis may be a source of genetic variation which drives evolution or a source of mutations with potential to cause dysfunction and disease
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Research Products
(31 results)
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[Journal Article] Hyper-Phosphorylated Retinoblastoma Protein Suppresses Telomere Elongation2008
Author(s)
Takemura, M., Sugimura, K., Okumura, K., Limsirichaikul, S., Suzuki, M., Yamada, Y., Yoshida, S
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Journal Title
Biosci. Biotech. Biochem (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ewing's sarcoma fusion protein, EWS/Fli-1 and Fli-1 protein induce PLD2 but not PLD1 gene expression by binding to an ETS domain of 5' promoter2007
Author(s)
Kikuchi, R., Murakami, M., Sobue, S., Iwasaki, T., Hagiwara, K., Takagi, A., Kojima, T., Asano, H., Suzuki, M., Banno, Y., Nozawa, Y., Murate, T
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Journal Title
Oncogene 26
Pages: 1802-1810
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mechanism of vitamin D(3) -induced transcription of phospholipase Dl in HaCat human keratinocytes2007
Author(s)
Kikuchi, R., Sobue, S., Murakami, M., Ito, H., Kimura, A., Iwasaki, T., Shibayama, S., Takagi, A., Kojima, T., Suzuki, M., Banno, Y., Nozawa, Y., Murate, T
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Journal Title
FEBS Lett 581
Pages: 1800-1801
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-922007
Author(s)
Matsubara, H., Takeuchi, T., Nishikawa, E., Yanagisawa, K., Hayashita, Y., Ebi, H., Yamada, H., Suzuki, M., Nagino, M., Nimura, Y., Osada, H., Takahashi, T
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Journal Title
Oncogene 26
Pages: 6099-6105
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] RET signaling-induced SPHK1 gene expression plays a role in both GDNF-induced differentiation and MEN2-type oncogenesis2007
Author(s)
Murakami, M., Ichihara, M., Sobue, S., Kikuchi, R., Ito, H., Kimura, A., Iwasaki, T., Takagi, A., Kojima, T., Takahashi, M., Suzuki, M., Banno, Y., Nozawa, Y., Murate, T
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Journal Title
J Neurochem 102
Pages: 1585-1594
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel NBS1 heterozygous germline mutation causing MRE11-binding domain loss predisposes to common types of cancer2007
Author(s)
Ebi, H., Matsuo, K., Sugito, H., Suzuki, M., Osada, H., Tajima, K., Ueda, R., Takahashi, T
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Journal Title
Cancer Res 67
Pages: 11158-65
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Evidence that errors made by DNA polymerase alpha are corrected by DNA polymerase delta2006
Author(s)
Pavlov, Y.I., Frahm, C., Nick, McElhinny, S. A., Niimi, A., Suzuki, M., Kunkel, T. A
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Journal Title
Curr Biol 16
Pages: 202-207
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Quantitative RT-PCR analysis of sphingolipid metabolic enzymes in acute leukemia and myelodysplastic syndromes2006
Author(s)
Sobue, S., Iwasaki, T., Sugisaki, C., Nagata, K., Kikuchi, R., Murakami, M., Takagi, A., Kojima, T., Banno, Y., Akao, Y., Nozawa, Y., Kannagi, R., Suzuki, M., Abe, A., Naoe, T., Murata, T
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Journal Title
Leukemia 20
Pages: 2042-2046
Description
「研究成果報告書概要(欧文)」より
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