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Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication
Author(s) -
Kobayashi Masahiko,
Hirano Atsushi,
Kumano Tomoyasu,
Xiang ShuangLin,
Mihara Keiko,
Haseda Yasunari,
Matsui Osamu,
Shimizu Hiroko,
Yamamoto Kenichi
Publication year - 2004
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1356-9597.2004.00728.x
Subject(s) - biology , dna damage , dna replication , g2 m dna damage checkpoint , control of chromosome duplication , microbiology and biotechnology , cell cycle checkpoint , dna re replication , dna , dna repair , genetics , chek1 , pre replication complex , gene , cell cycle
The Rad17‐replication factor C (Rad17‐RFC) and Rad9‐Rad1‐Hus1 complexes are thought to function in the early phase of cell‐cycle checkpoint control as sensors for genome damage and genome replication errors. However, genetic analysis of the functions of these complexes in vertebrates is complicated by the lethality of these gene disruptions in embryonic mouse cells. We disrupted the Rad17 and Rad9 loci by gene targeting in the chicken B lymphocyte line DT40. Rad17 −/− and Rad9 −/− DT40 cells are viable, and are highly sensitive to UV irradiation, alkylating agents, and DNA replication inhibitors, such as hydroxyurea. We further found that Rad17 −/− and Rad9 −/− but not ATM −/− cells are defective in S‐phase DNA damage checkpoint controls and in the cellular response to stalled DNA replication. These results indicate a critical role for chicken Rad17 and Rad9 in the cellular response to stalled DNA replication and DNA damage.