POT1-TPP1 telomere length regulation and disease

Abstract

Telomeres are DNA repeats at the ends of linear chromosomes and are replicated by telomerase, a ribonucleoprotein reverse transcriptase. Telomere length regulation and chromosome end capping are essential for genome stability and are mediated primarily by the shelterin and CST complexes. POT1-TPP1, a subunit of shelterin, binds the telomeric overhang, suppresses ATR-dependent DNA damage response, and recruits telomerase to telomeres for DNA replication. POT1 localization to telomeres and chromosome end protection requires its interaction with TPP1. Therefore, the POT1-TPP1 complex is critical to telomere maintenance and full telomerase processivity. The aim of this mini-review is to summarize recent POT1-TPP1 structural studies and discuss how the complex contributes to telomere length regulation. In addition, we review how disruption of POT1-TPP1 function leads to human disease.

Keywords: ATM, Ataxia Telangiectasia Mutated protein; ATR, Ataxia Telangiectasia and Rad3-related Protein; CST, CTC1, Stn1 and Ten1; CTC1, Conserved Telomere Capping Protein 1; POT1; POT1, Protection of telomere 1; RAP1, Repressor/Activator Protein 1; RPA, Replication Protein A; SMCHD1, Structural Maintenance Of Chromosomes Flexible Hinge Domain Containing 1; Shelterin; Stn1, Suppressor of Cdc Thirteen; TERC, Telomerase RNA; TERT, Telomerase Reverse Transcriptase; TIN2, TRF1- and TRF2-Interacting Nuclear Protein 2; TPP1; TPP1 also known as ACD, Adrenocortical Dysplasia Protein Homolog; TRF1, Telomere Repeat binding Factor 1; TRF2, Telomere Repeat binding Factor 2; TSPYL5, Testis-specific Y-encoded-like protein 5; Telomerase; Telomeres; Ten1, Telomere Length Regulation Protein; USP7, ubiquitin-specific-processing protease 7.