biostudies-literatureUnknown102(27)Ishii HWe 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 surProceedings of the National Academy of Sciences of the United States of America9655-60https://www.ebi.ac.uk/biostudies/studies/S-EPMC1172282biostudies-literatureFrag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis.PMC1172282Mori MInageta TOzawa KSaito TFurukawa YSasaki HCroce CMIshii HMimori KHuebner KIsobe MfalseFrag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis.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 sur2005-01-01T00:00:00Z2005 Jul2026-05-30T08:47:10.73Z2019-03-27T01:09:06ZS-EPMC11722821598338710.1073/pnas.0504222102