Multifunctional Role of ATM/Tel1 Kinase in Genome Stability: From the DNA Damage Response to Telomere Maintenance

Figure 3

Telomere structure in human and S. cerevisiae. Human telomeres consist of kilobases of TTAGGG repeats, ending with a 3′ overhang, G-rich strand. The shelterin complex includes six proteins: TRF1 and TRF2, which bind directly the double-stranded telomeric DNA and are held together by TIN2, RAP1 that interacts with TRF2, POT1 that associates with telomeric ssDNA, and TPP1. These factors mediate the generation of higher-order structure at chromosome ends (T-loop) by invasion of the single-stranded G-overhang into the double-stranded TTAGGG repeats. In Budding yeast, the double-stranded telomeric sequence is bound by Rap1, which regulates telomere length together with Rif1 and Rif2. Cdc13 Ten1 and Stn1 bind to the single strand overhang. In both human and S. cerevisiae, the heterodimeric Ku complex (Ku70/80) interacts with the terminal part of the telomere, providing a protective role. The heterotrimeric complex MRX/MRN (MRE11/Mre11, RAD50/Rad50, and NBS1/Xrs2) promotes ATM/Tel1 recruitment, with a central role in telomere capping and length regulation.