Involvement of topoisomerase III in telomere-telomere recombination.
Telomere maintenance is required for chromosome stability, and telomeres are typically replicated by the action of telomerase. In both mammalian tumor and yeast cells that lack telomerase, telomeres are maintained by an alternative (ALT) recombination mechanism. In yeast, Sgs1p and its associated type IA topoisomerase, Top3p, may work coordinately in removing Holliday junction intermediates from a crossover-producing recombination pathway. Previous studies have also indicated that Sgs1 helicase acts in a telomere recombination pathway. Here we show that topoisomerase III is involved in telomere-telomere recombination. The recovery of telomere recombination-dependent survivors in a telomerase-minus yeast strain was dependent on Top3p catalytic activity. Moreover, the RIF1 and RIF2 genes are required for the establishment of TOP3/SGS1-dependent telomere-telomere recombination. In human Saos-2 ALT cells, human topoisomerase IIIalpha (hTOP3alpha) also contributes to telomere recombination. Strikingly, the telomerase activity is clearly enhanced in surviving si-hTOP3alpha Saos-2 ALT cells. Altogether, the present results suggest a potential role for hTOP3alpha in dissociating telomeric structures in telomerase-deficient cells, providing therapeutic implications in human tumors.
Tsai
Hung-Ji
HJ
Department of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei 10018, Taiwan.
Huang
Wei-Hsiang
WH
Department of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei 10018, Taiwan.
Li
Tsai-Kun
TK
Department of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei 10018, Taiwan.
Tsai
Yun-Luen
YL
Department of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei 10018, Taiwan.
Wu
Kou-Juey
KJ
Institute of Biochemistry, National Yang-Ming University, Taipei 11221, Taiwan.
Tseng
Shun-Fu
SF
Department of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei 10018, Taiwan.
Teng
Shu-Chun
SC
Department of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei 10018, Taiwan; Institute of Internal Medicine, National Taiwan University Hospital, Taipei 10018, Taiwan. Electronic address: scteng@ha.mc.ntu.edu.tw.
D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C105362:RIF2 protein, S cerevisiae; D012097:Repressor Proteins; C492743:Rif1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C074461:RIF1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C505365:Sps1 protein, S cerevisiae; D019098:Telomerase; D004264:DNA Topoisomerases, Type I