RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway.
Budding yeast Cdc13, Stn1, and Ten1 form the CST complex to protect telomeres from lethal DNA degradation. It remains unknown whether similar complexes are conserved in higher eukaryotes or not. Here we isolated mammalian STN1 and TEN1 homologs and CTC1 (conserved telomere maintenance component 1). The three proteins contain putative OB-fold domains and form a complex called CST, which binds to single-stranded DNA with high affinity in a sequence-independent manner. CST associates with a fraction of telomeres consistently during the cell cycle, in quiescent cells and Pot1-knockdown cells. It does not colocalize with replication foci in S phase. Significant increases in the abundance of single-stranded G-strand telomeric DNA were observed in Stn1-knockdown cells. We propose that CST is a replication protein A (RPA)-like complex that is not directly involved in conventional DNA replication at forks but plays a role in DNA metabolism frequently required by telomeres.
Laboratory of Cell Cycle Regulation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Yasuyuki
Y
Miyake
Mirai
M
Nakamura
Akira
A
Nabetani
Shintaro
S
Shimamura
Miki
M
Tamura
Shin
S
Yonehara
Motoki
M
Saito
Fuyuki
F
Ishikawa
D000818:Animals; D001483:Base Sequence; D004277:DNA, Single-Stranded / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011994:Recombinant Proteins; D051716:Replication Protein A / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D000089804:Shelterin Complex; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
C544945:Ctc1 protein, human; D004277:DNA, Single-Stranded; D046912:Multiprotein Complexes; D050505:Mutant Proteins; C440849:POT1 protein, human; D011994:Recombinant Proteins; D051716:Replication Protein A; D000089804:Shelterin Complex; C544946:Stn1 protein, human; D034501:Telomere-Binding Proteins; C544947:Ten1 protein, human