Activation of S phase checkpoint by cigarette smoke extract in Schizosaccharomyces pombe.
Cigarette smoke has long been recognized as a major environmental pollutant that can cause significant damage to the cellular macromolecules. Although much is known about the types of damage, little is known about the cellular responses to the stress caused by cigarette smoke. We have used the fission yeast Schizosaccharomyces pombe to elucidate the overall cellular responses towards cigarette smoke. Here, we demonstrate that fission yeast cells exposed to aqueous extract of cigarette smoke exhibit cell cycle arrest and cell death in a dose-dependent manner. Cigarette smoke treatment also results in accumulation of reactive oxygen species, unusual nuclear morphology and altered cellular structure. Our data further establish activation of the S phase checkpoint in cigarette smoke-exposed Sz. pombe cells. The checkpoint proteins Rad3, Rad26, Rad17, Rad1, Hus1 and Cds1 play key roles in this process, as evidenced by cell survival and biochemical analysis, although another checkpoint protein, Rad9, seems to be less required. Our results also suggest involvement of the stress-activated protein kinase Spc1/Sty1 and the bZIP transcription factors Atf1 and Pap1 in the cellular response towards cigarette smoke extract. These findings indicate activation of the critical S phase checkpoint and cell cycle arrest in Sz. pombe following CSE assault.
Chaudhuri
Santanu Pal
SP
Dr B.C. Guha Centre for Genetic Engineering and Biotechnology, Department of Biochemistry, University of Calcutta, 35 B.C. Road, Kolkata 700019, India.
Sundaram
Geetanjali
G
Bhattacharya
Abhishek
A
Ray
Partha
P
Ray
Anirban
A
Chatterjee
Indu Bhushan
IB
Chattopadhyay
Dhrubajyoti
D
D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D015966:Gene Expression Regulation, Fungal; D018869:Heat-Shock Response; D000073718:Pancreatitis-Associated Proteins; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016196:S Phase / Q000187:drug effects*; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects* / Q000737:chemistry
D018797:Cell Cycle Proteins; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D017382:Reactive Oxygen Species; D029702:Schizosaccharomyces pombe Proteins; D012906:Smoke; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578636:Cds1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; C456840:rad3 protein, S pombe