2013 Fiscal Year Final Research Report
Roles of replication stress for cellular senescence and genome instability in preneoplastic lesions
| Project/Area Number |
23501257
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Carcinogenesis
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| Research Institution | Gunma University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ODA Tsukasa 群馬大学, 生体調節研究所, 助教 (10323643)
SEKIMOTO Takayuki 群馬大学, 生体調節研究所, 助教 (20436322)
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| Project Period (FY) |
2011 – 2013
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| Keywords | DNA複製 / DNA複製ストレス / Y-family polymerase / cyclin E / geminin / ゲノム不安定性 / 前がん病変 / 発がん |
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| Research Abstract |
In preneoplastic lesions, oncogene-induced replication stress plays a dual role induction of cell senescence/apoptosis and tumor promotion through increased genomic instability. In these processes, oncogene-induced excessive activation of replication origins and consequent rereplication plays a major role. However, little is known about fork progression during rereplication. When rereplication was induced by depletion of geminin, a regulator of origin activation, Pol-eta was recruited to rereplication sites in human cell lines. Similar observations were obtained in cyclin E-induced rereplication in human tumor cells. Furthermore, Pol-eta knockdown suppressed rereplication induced by either geminin depletion or cyclin E expression. Together, our data suggest that Pol-eta participates in oncogene-induced rereplication. These findings provide important mechanistic insights into genomic instability during tumorigenesis.
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Research Products
(17 results)
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[Journal Article] Matched sibling donor stem cell transplantation for Fanconi anemia patients with T-cell somatic mosaicism2012
Author(s)
Yabe M, Shimizu T, Morimoto T, Koike T, Takakura H, Tsukamoto H, Muroi K, Oshima K, Asami K, Takata M, Yamashita T, Kato S, Yabe H
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Journal Title
Pediatr Transplant
Volume: 16
Pages: 340-345
DOI
Peer Reviewed
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[Journal Article] Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL112011
Author(s)
Sasaki M, Kawahara K, Nishio M, Mimori K, Kogo R, Hamada K, Itoh B, Wang J, Komatsu Y, Yang YR, Hikasa H, Horie Y, Yamashita T, Kamijo T, Zhang Y, Zhu Y, Prives C, Nakano T, Mak TW, Sasaki T, Maehama T, Mori M, Suzuki A
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Journal Title
Nat Med
Volume: 17
Pages: 944-951
DOI
Peer Reviewed
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