RRC ID 30237
著者 Miyagawa K, Low RS, Santosa V, Tsuji H, Moser BA, Fujisawa S, Harland JL, Raguimova ON, Go A, Ueno M, Matsuyama A, Yoshida M, Nakamura TM, Tanaka K.
タイトル SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1(Tpp1) to modulate shelterin-Stn1 interaction in fission yeast.
ジャーナル Proc Natl Acad Sci U S A
Abstract Telomeres protect DNA ends of linear eukaryotic chromosomes from degradation and fusion, and ensure complete replication of the terminal DNA through recruitment of telomerase. The regulation of telomerase is a critical area of telomere research and includes cis regulation by the shelterin complex in mammals and fission yeast. We have identified a key component of this regulatory pathway as the SUMOylation [the covalent attachment of a small ubiquitin-like modifier (SUMO) to target proteins] of a shelterin subunit in fission yeast. SUMOylation is known to be involved in the negative regulation of telomere extension by telomerase; however, how SUMOylation limits the action of telomerase was unknown until now. We show that SUMOylation of the shelterin subunit TPP1 homolog in Schizosaccharomyces pombe (Tpz1) on lysine 242 is important for telomere length homeostasis. Furthermore, we establish that Tpz1 SUMOylation prevents telomerase accumulation at telomeres by promoting recruitment of Stn1-Ten1 to telomeres. Our findings provide major mechanistic insights into how the SUMOylation pathway collaborates with shelterin and Stn1-Ten1 complexes to regulate telomere length.
巻・号 111(16)
ページ 5950-5
公開日 2014-4-22
DOI 10.1073/pnas.1401359111
PII 1401359111
PMID 24711392
PMC PMC4000806
MeSH Carrier Proteins / metabolism* DNA-Binding Proteins G2 Phase Ligases Lysine / metabolism Models, Biological Protein Binding Protein Subunits / metabolism* S Phase Schizosaccharomyces / cytology Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / metabolism* Sumoylation* Telomerase / metabolism Telomere / metabolism* Telomere Homeostasis* Telomere Shortening Telomere-Binding Proteins / metabolism* Ubiquitin-Protein Ligases / metabolism
IF 9.412
引用数 32
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
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