Telomere Biology: A New Player in the End Zone

Cancer Research Unit, Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, Sydney, NSW 2145, Australia.
Current Biology (Impact Factor: 9.57). 11/2004; 14(20):R901-2. DOI: 10.1016/j.cub.2004.09.075
Source: PubMed


Yet another protein has been added to the crowd of players found at the ends of chromosomes. Known variously as PTOP, PIP1 or TINT1, this negative regulator of telomere length connects some of the key proteins already known to be present - TRF1, TIN2, POT1, and TRF2 - and adds even more complexity to telomere protein interactions.

Download full-text


Available from: Lorel Colgin, Jul 07, 2014
13 Reads
  • Source
    • "Telomeres are the specialized protective nucleoprotein complexes which protect the end of eukaryotic chromosome from end-to-end fusion between chromosome termini [1] [2]. Collapse of telomere length homeostasis is implicated in aging and cancer [1]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The telomeric repeat binding protein 1(TRF1) is a major factor of the mammalian telosome/shelterin and negatively regulates telomere length by inhibiting access of telomerase at telomere termini in telomerase-positive cells. In telomerase-negative cancer cells, TRF1 also plays a critical role in the mechanism called alternative lengthening of telomeres (ALT) and is essential for formation of the ALT-associated PML bodies (APBs). It was reported that TRF1 can be degraded by the ubiquitin-proteasome pathway, involving in two regulation factors, Fbx4 and RLIM. Here, we reported that β-TrCP1, a member of the F-box family protein with ubiquitin ligase activity, is a novel TRF1-associating protein. β-TrCP1 interacts with TRF1 in vivo and in vitro and promotes its ubiquitination. Overexpression of β-TrCP1 reduces endogenous TRF1 protein levels, while inhibition of β-TrCP1 by siRNA stabilizes TRF1. Moreover, we found that β-TrCP1 is essential for regulation of promyelocytic leukemia body recruitment of TRF1 in U2OS cells. These results reveal that β-TrCP1 is involved in the negative regulation of TRF1 and represents a new pathway for APB formation in telomerase-negative cells.
    Biochemical and Biophysical Research Communications 04/2013; 434(4). DOI:10.1016/j.bbrc.2013.03.096 · 2.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The circular dichroism, CD, spectra of the telomere repeats of vertebrates, d(TTAGGG), indicate that parallel type quadruplex structures or disordered single-stranded structures are formed in low salt. Anti-parallel quadruplex structures are favored in the presence of high concentrations, 140 mM, of sodium. External loop, also known as propeller, parallel type structures are favored in the presence of high concentrations, 100 mM, of potassium in the presence of either 5 or 140 mM sodium. The cation dependence of the CD spectra of the vertebrate telomere repeat DNAs is distinctly different from that of the telomere repeats of Tetrahymena and Oxytricha as well as that of the thrombin binding aptamer. These results indicate that the external loop structures may be present in vertebrate telomeres under the conditions of high potassium and low sodium concentration found in nuclei.
    Nucleic Acids Research 02/2005; 33(6):2022-31. DOI:10.1093/nar/gki345 · 9.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To maintain chromosomal integrity and to protect the ends of chromosomes against recognition as damaged DNA, end-to-end fusion, or recombination, a coordinated set of genes is required to stabilize the telomere. We surveyed common genetic variation in seven genes that are vital to telomere stability (TERT, POT1, TNKS, TERF1, TINF2, TERF2, and TERF2IP) and validated single nucleotide polymorphisms (SNPs) in four different ethnic groups (n=118 total). Overall, our data show limited degrees of nucleotide diversity in comparison with data from other gene families. We observed that these genes are highly conserved in sequence between species, and that for nearly all of the coding SNPs the most common allele is ancestral (i.e., it is observed in primate sequences). Our findings support the hypothesis that genetic variation in a pathway that is critical for telomere stability may be under constraint. These data establish a foundation for further investigation of these genes in population-genetics, evolution, and disease-association studies.
    Human Mutation 10/2005; 26(4):343-50. DOI:10.1002/humu.20226 · 5.14 Impact Factor
Show more