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PMID:15983387
| Citation |
Ishii, H, Inageta, T, Mimori, K, Saito, T, Sasaki, H, Isobe, M, Mori, M, Croce, CM, Huebner, K, Ozawa, K and Furukawa, Y (2005) Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis. Proc. Natl. Acad. Sci. U.S.A. 102:9655-60 |
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| 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. |
| Links |
PubMed PMC1172282 Online version:10.1073/pnas.0504222102 |
| Keywords |
Amino Acid Sequence; Animals; Apoptosis/genetics; Base Sequence; Blotting, Northern; Bromodeoxyuridine; Cell Cycle Proteins/metabolism; Cells, Cultured; Chromatin/metabolism; DNA Damage/genetics; Flow Cytometry; Gene Expression Regulation; Genomic Instability/genetics; Humans; Immunoprecipitation; Mice; Molecular Sequence Data; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Plasmids/genetics; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism; RNA, Small Interfering/genetics; S Phase/physiology; Sequence Analysis, DNA; Signal Transduction/genetics; bcl-2-Associated X Protein |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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