SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1(Tpp1) to modulate shelterin-Stn1 interaction in fission yeast

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...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-04, Vol.111 (16), p.5950-5955
Main Authors: Miyagawa, Keisuke, Low, Ross S, Santosa, Venny, Tsuji, Hiroki, Moser, Bettina A, Fujisawa, Shiho, Harland, Jennifer L, Raguimova, Olga N, Go, Andrew, Ueno, Masaru, Matsuyama, Akihisa, Yoshida, Minoru, Nakamura, Toru M, Tanaka, Katsunori
Format: Article
Language:English
Subjects:
Carrier Proteins - metabolism
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
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1091-6490
DOI:10.1073/pnas.1401359111