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TPP1 as a versatile player at the ends of chromosomes |
Sijie ZHANG1,2,Zhenhua LUO1,2,Guang SHI1,2,Dan LIU3,4,Zhou SONGYANG1,2,4,*( ),Junjiu HUANG1,2,*() |
1. Key Laboratory of Reproductive Medicine of Guangdong Province, the First Affiliated Hospital and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
2. SYSU-BCM Joint Research Center for Biomedical Sciences, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
3. Cell-Based Assay Screening Core, Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
4. Verna and Marrs Mclean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA |
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Abstract Telomeres, the ends of linear eukaryotic chromosomes, are tandem DNA repeats and capped by various telomeric proteins. These nucleoprotein complexes protect telomeres from DNA damage response (DDR), recombination, and end-to-end fusions, ensuring genome stability. The human telosome/shelterin complex is one of the best-studied telomere-associated protein complexes, made up of six core telomeric proteins TRF1, TRF2, TIN2, RAP1, POT1, and TPP1. TPP1, also known as adrenocortical dysplasia protein homolog (ACD), is a putative mammalian homolog of TEBP-β and belongs to the oligonucleotide binding (OB)-fold-containing protein family. Three functional domains have been identified within TPP1, the N-terminal OB fold, the POT1 binding recruitment domain (RD), and the carboxyl-terminal TIN2-interacting domain (TID). TPP1 can interact with both POT1 and TIN2 to maintain telomere structure, and mediate telomerase recruitment for telomere elongation. These features have indicated TPP1 play an essential role in telomere maintenance. Here, we will review important findings that highlight the functional significance of TPP1, with a focus on its interaction with other telosome components and the telomerase. We will also discuss potential implications in disease therapies.
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telomere
TPP1
TIN2
telosome/shelterin
telomerase
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Corresponding Author(s):
Zhou SONGYANG
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Issue Date: 24 June 2014
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