Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment

• DOI: 10.1073/pnas.1217733110
• Publication Date: 2013-03-19T07:06:17Z
• Authors: Yi Zhang; Liuh-Yow Chen; Xin Han; Wei Xie; Hyeung Kim; Dong Yang; Dan Liu; Zhou Songyang
• Keywords: Telomere-binding protein

Telomere maintenance is essential for organisms with linear chromosomes and carried out by telomerase during cell cycle. The precise mechanism which cycle controls telomeric access of telomere elongation in mammals remains largely unknown. Previous work has established oligonucleotide/oligosaccharide binding (OB) fold-containing protein TPP1, formerly known as TINT1, PTOP, PIP1, a key factor that regulates recruitment activity. However, the role TPP1 cycle-dependent unclear. Here, we report human phosphorylated at multiple sites progression associates higher activity late S/G 2 /M. Phosphorylation Ser111 (S111) within OB fold appears important recruitment. Structural analysis indicates S111 resides telomerase-interacting domain fold. Mutations disrupt phosphorylation led to decreased complex shortening. Our findings provide insight into regulatory pathways structural basis control through TPP1.