RRC ID 29221
著者 Belfield C, Queenan C, Rao H, Kitamura K, Walworth NC.
タイトル The oxidative stress responsive transcription factor Pap1 confers DNA damage resistance on checkpoint-deficient fission yeast cells.
ジャーナル PLoS One
Abstract Eukaryotic cells invoke mechanisms to promote survival when confronted with cellular stress or damage to the genome. The protein kinase Chk1 is an integral and conserved component of the DNA damage response pathway. Mutation or inhibition of Chk1 results in mitotic death when cells are exposed to DNA damage. Oxidative stress activates a pathway that results in nuclear accumulation of the bZIP transcription factor Pap1. We report the novel finding that fission yeast Pap1 confers resistance to drug- and non-drug-induced DNA damage even when the DNA damage checkpoint is compromised. Multi-copy expression of Pap1 restores growth to chk1-deficient cells exposed to camptothecin or hydroxyurea. Unexpectedly, increased Pap1 expression also promotes survival of chk1-deficient cells with mutations in genes encoding DNA ligase (cdc17) or DNA polymerase δ (cdc6), but not DNA replication initiation mutants. The ability of Pap1 to confer resistance to DNA damage was not specific to chk1 mutants, as it also improved survival of rad1- and rad9-deficient cells in the presence of CPT. To confer resistance to DNA damage Pap1 must localize to the nucleus and be transcriptionally active.
巻・号 9(2)
ページ e89936
公開日 2014-1-1
DOI 10.1371/journal.pone.0089936
PII PONE-D-13-50101
PMID 24587136
PMC PMC3934961
MeSH Basic-Leucine Zipper Transcription Factors / genetics Basic-Leucine Zipper Transcription Factors / metabolism* Camptothecin Cell Nucleus / metabolism* Checkpoint Kinase 1 DNA Damage / genetics* DNA Ligases / genetics Hydroxyurea Microscopy, Fluorescence Oxidative Stress / genetics Oxidative Stress / physiology* Pancreatitis-Associated Proteins Protein Kinases / deficiency* Schizosaccharomyces / genetics Schizosaccharomyces / physiology* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism*
IF 2.74
引用数 6
WOS 分野 CELL BIOLOGY
リソース情報
酵母 genome library (pTN-L1)