Item type |
デフォルトアイテムタイプ_(フル)(1) |
公開日 |
2023-03-18 |
タイトル |
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タイトル |
Haploinsufficiency of the Mus81.Eme1 endonuclease activates the intra-S-phase and G2/M checkpoints and promotes rereplication in human cells |
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言語 |
en |
作成者 |
Hiyama, Takashi
Katsura, Mari
Yoshihara, Takashi
Ishida, Mari
Kinomura, Aiko
Tonda, Tetsuji
Asahara, Toshimasa
Miyagawa, Kiyoshi
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アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
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権利情報 |
Copyright (c) 2006 Oxford University Press. |
主題 |
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主題Scheme |
NDC |
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主題 |
490 |
内容記述 |
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内容記述 |
The Mus81.Eme1 complex is a structure-specific endonuclease that preferentially cleaves nicked Holliday junctions, 3'-flap structures and aberrant replication fork structures. Mus81-/- mice have been shown to exhibit spontaneous chromosomal aberrations and, in one of two models, a predisposition to cancers. The molecular mechanisms underlying its role in chromosome integrity, however, are largely unknown. To clarify the role of Mus81 in human cells, we deleted the gene in the human colon cancer cell line HCT116 by gene targeting. Here we demonstrate that Mus81 confers resistance to DNA crosslinking agents and slight resistance to other DNA-damaging agents. Mus81 deficiency spontaneously promotes chromosome damage such as breaks and activates the intra-S-phase checkpoint through the ATM-Chk1/Chk2 pathways. Furthermore, Mus81 deficiency activates the G2/M checkpoint through the ATM-Chk2 pathway and promotes DNA rereplication. Increased rereplication is reversed by the ectopic expression of Cdk1. Haploinsufficiency of Mus81 orEme1 also causes similar phenotypes.These findings suggest that a complex network of the checkpoint pathways that respond to DNA doublestrand breaks may participate in some of the phenotypes associated with Mus81 or Eme1 deficiency. |
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言語 |
en |
出版者 |
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出版者 |
Oxford University Press |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
10.1093/nar/gkj495 |
関連情報 |
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識別子タイプ |
PMID |
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関連識別子 |
16456034 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
http://dx.doi.org/10.1093/nar/gkj495 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0305-1048 |
収録物識別子 |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA00760269 |
開始ページ |
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開始ページ |
880 |
書誌情報 |
Nucleic Acids Research
Nucleic Acids Research
巻 34,
号 3,
p. 880-892,
発行日 2006
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旧ID |
17113 |