Functional relationships between Rad18 and WRNIP1 in vertebrate cells.
The WRNIP1 protein interacts with WRN, the product of the causative gene for Werner syndrome. Mutation of the Saccharomyces cerevisiae gene MGS1, the yeast counterpart of WRNIP1, confers synthetic lethality with mutation of RAD18. To examine the functional relationship between WRNIP1 and Rad18 in higher eukaryotic cells, we generated WRNIP1-/-/-/RAD18-/- lines from chicken DT40 cells and compared them with single mutant cell lines. Unlike the corresponding yeast mutant, WRNIP1-/-/-/RAD18-/- cells are viable but grow more slowly than single mutants and wild type cells, and they show an additive or synergistic elevation in the frequency of sister chromatid exchanges. As reported, WRNIP1-/-/- cells and RAD18-/- cells are moderately and severely sensitive to camptothecin (CPT), respectively. Unexpectedly, the severe CPT sensitivity of RAD18-/- cells is slightly suppressed by disruption of the WRNIP1 gene.
Yoshimura
Akari
A
Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Seki
Masayuki
M
Hayashi
Tomoko
T
Kusa
Yumiko
Y
Tada
Shusuke
S
Ishii
Yutaka
Y
Enomoto
Takemi
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002166:Camptothecin / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002645:Chickens; D002945:Cisplatin / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009154:Mutation / Q000235:genetics*; D011995:Recombination, Genetic / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases
D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C485954:RAD18 protein, human; D008741:Methyl Methanesulfonate; D044767:Ubiquitin-Protein Ligases; D002945:Cisplatin; D002166:Camptothecin