title: A novel role for Rad17 in homologous recombination.
abstract: Replication checkpoint protein Rad17 senses DNA lesions during DNA replication and halts progression of replication fork. The cells derived from Bloom syndrome individuals show some defects in DNA replication. In order to investigate the functional relationship between the replication checkpoint protein Rad17 and BLM, which is the product of the causative gene of Bloom syndrome, we generated BLM/RAD17 double knockout (blm/rad17) cells using chicken DT40 cells. The blm/rad17 cells showed exaggerated growth defects as determined by analysis of their growth curves and plating efficiency compared to those of either of the single gene mutants. These defects seem to be due to an increase in DNA lesions that cause spontaneous cell death, suggesting that Rad17 and BLM execute different functions in the progression of replication forks. We also demonstrate that targeting integration was dramatically compromised by a lack of Rad17. In addition, the elevated frequency of sister chromatid exchange (SCE) due to homologous recombination in BLM knockout (blm) cells was greatly reduced by disruption of the RAD17 gene. Thus, in addition to its role in the replication checkpoint, Rad17 appears to play a role in homologous recombination.
authors.affiliation: Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Nishino
authors.forename: Eri
authors.initials: E
authors.lastname: Inoue
authors.forename: Shunya
authors.initials: S
authors.lastname: Takada
authors.forename: Takuya
authors.initials: T
authors.lastname: Abe
authors.forename: Motomu
authors.initials: M
authors.lastname: Akita
authors.forename: Akari
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Shusuke
authors.initials: S
authors.lastname: Tada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Seki
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
mesh_terms: D000818:Animals; D001816:Bloom Syndrome / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange
chemical_list: D018797:Cell Cycle Proteins; C097151:Bloom syndrome protein; D053484:RecQ Helicases