TPP1 as a versatile player at the ends of chromosomes  

作　　者：Sijie ZHANG 

机构地区：[1]Key Laboratory of Reproductive Medicine of Guangdong Province, the First Affiliated Hospital and Key Laboratory of Gene Engineering ofthe 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, TX77030, USA

出　　处：《Frontiers in Biology》2014年第3期225-233,共9页生物学前沿（英文版）

基　　金：Acknowledgements This study was supported by the National Basic Research Program （973 Program） （Nos. 2012CB911201 and 2010CB945401）, the National Natural Science Foundation （Grant Nos. 31371508, 91019020 and 81330055）, the Introduced Innovative R and D Team of Guangdong Province （No. 201001Y0104687244）, Zhujiang Program of Science and Technology Nova in Guangzhou （No. 2011 J2200082）.

摘　　要：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, RAPI, POT1, and TPPI. 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.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, RAPI, POT1, and TPPI. 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.

关 键 词：TELOMERE TPP1 TIN2 telosome/shelterin TELOMERASE 

分 类 号：Q344.2[生物学—遗传学] Q523