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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sasaki, Hiroki Ozawa, Keiya Mimori, Koshi Croce, Carlo M. Furukawa, Yusuke Inageta, Taeko Mori, Masaki Ishii, Hideshi Saito, Toshiyuki Isobe, Masaharu Huebner, Kay |
| Description | Author Affiliation: Ishii H ( Center for Molecular Medicine, Jichi Medical School, Tochigi 329-0498, Japan.); |
| Abstract | We report the identification and characterization of a potent regulator of genomic integrity, mouse and human FRAG1 gene, a conserved homolog of replication factor C large subunit that is homologous to the alternative replication factor C subunits Elg1, Ctf18/Chl12, and Rad24 of budding yeast. FRAG1 was identified in a search for key caretaker genes involved in the regulation of genomic stability under conditions of replicative stress. In response to stress, Atr participates in the down-regulation of FRAG1 expression, leading to the induction of apoptosis through the release of Rad9 from damaged chromatin during the S phase of the cell cycle, allowing Rad9-Bcl2 association and induction of proapoptotic Bax protein. We propose that the Frag1 signal pathway, by linking replication stress surveillance with apoptosis induction, plays a central role in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 27 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Genetics DNA Damage Gene Expression Regulation Genomic Instability Nuclear Proteins Signal Transduction Amino Acid Sequence Animals Ataxia Telangiectasia Mutated Proteins Blotting, Northern Bromodeoxyuridine Cell Cycle Proteins Metabolism Cells, Cultured Chromatin Flow Cytometry Immunoprecipitation Mice Molecular Sequence Data Plasmids Protein-Serine-Threonine Kinases Proto-Oncogene Proteins C-bcl-2 RNA, Small Interfering S Phase Physiology Sequence Analysis, DNA Bcl-2-Associated X Protein Comparative Study Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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