Telomere shortening by cisplatin in yeast nucleotide excision repair mutant.
Telomeres are unique DNA tandem repeats that form the ends of eukaryotic chromosomes to protect the chromosomes from degradation and illegitimate recombination. In yeast, loss of telomere may be compensated for through the acquisition of new telomere by RAD52-mediated or RAD52-independent recombinational repair. In this report, the effects of cis-dichlorodiammine-platinum (II) (cisplatin) on telomere length and the role of nucleotide excision repair in telomere maintenance were examined in the yeast Saccharomyces cerevisiae. We showed that the SSL2 (RAD25) DNA repair yeast mutant exhibited a gradual shortening of the telomere in the presence of cisplatin. Further telomere shortening was prevented upon the withdrawal of cisplatin. Complementation of the mutant with the wild-type SSL2 (RAD25) gene abolished the cisplatin-induced telomere degradation. These results suggest that telomeres are susceptible to cisplatin-induced intrastrand crosslinks and that Ssl2 (Rad25) or the nucleotide excision repair pathway may play a critical role in the repair and the maintenance of telomere integrity.
Ishii
K
K
The Cancer Institute of New Jersey, Department of Medicine, Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, New Jersey 08901, USA.
Yang
W L
WL
Cvijic
M E
ME
Kikuchi
Y
Y
Nagata
I
I
Chin
K V
KV
D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair; D004271:DNA, Fungal / Q000187:drug effects*; D005656:Fungal Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016615:Telomere / Q000187:drug effects*; D051758:Transcription Factor TFIIH
D004271:DNA, Fungal; D005656:Fungal Proteins; C489575:SSL2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D051758:Transcription Factor TFIIH; D004265:DNA Helicases; D002945:Cisplatin