Fig. 4.

Gene expression levels of shelterin complex genes in breast cancer (TCGA TARGET GTEx RNAseq data) and their link to DDR A. Cartoon describing that shelterin complex consists of majorly six proteins – TERF1, TERF2, Rap1, TIN2, TPP1, and POT1. TERF1 and TERF2 are homodimers binding to the double-stranded telomeric DNA through the Myb domain. Rap1 is an interactive partner of TERF2. TPP1 and POT1 bind to the ssDNA telomere and protect the 3′ overhang sequence of the telomere. TIN2 acts as a bridge between TERF1/TERF2 and TPP1/POT1 and stabilizes the shelterin complex. TERF2 and POT1 block ATM and ATR kinase respectively through which shelterin complex sequesters telomere from DDR, mainly initiated by activation of ATM and ATR kinases resulting in DNA repair mechanisms. B. Shelterin complex genes mRNA expression levels of shelterin complex genes were compared between “normal” (GTEx) and tumor samples (TCGA). The middle line in the boxes represents the median value. Graph-pad Prism software was used to calculate statistical differences by two-tailed Student's t-test. ****P < 0.00001.

TERF1, telomeric repeat-binding factor 1; TERF2, telomeric repeat-binding factor 2; Rap1/TERF2IP, telomeric-repeating binding factor 2-interacting factor; POT1, protection of telomeres protein 1; TPP1/ACD; Adrenocortical dysplasia protein; TIN2/TINF2, TERF1-interacting nuclear factor 2; DDR, DNA damage response, ATM, Ataxia telangiectasia mutated kinase; ATR, Ataxia telangiectasia, and Rad3.