Dynamic model of DNA damage signals generated by short telomeres.
Following replication and processing, a chromosome end with a G-rich single-strand overhang is created (A). This structure is processed and bound by various telomere binding proteins, including hPOT16 (indicated by the small clear circle), which binds to the 3′ single-strand overhang, and TRF1 and TRF2 (indicated by light and dark gray circles), which are capable of folding telomeric DNA.32 If the length of telomere repeats is sufficiently long (L), double-stranded telomere repeats can easily fold back onto the single-strand overhang, resulting in a relatively stable structure.7 The stability of the poorly understood fold-back structure could be compromised when telomeres are short (S), resulting in a shift of the equilibrium between capped and uncapped telomeres4 that is independent of DNA replication.
