Telomeres Do D-Loop–T-Loop

has suggested that telomere-binding proteins provide these functions. Telomere-Binding Proteins. The binding proteins that mediate telomere function come in two flavors: double-stranded DNA-binding proteins and single-stranded DNA end–binding proteins. The best-characterized end-Rarely it seems does a new result emerge, loop around, binding protein is the ␣/␤ heterodimer protein from Oxy-and bite you from behind. But a collaboration between tricha (reviewed in Fang and Cech, 1995). This protein Jack Griffith's and Titia de Lange's laboratories to look binds tightly to the single-stranded regions of the G at the binding of telomere proteins to telomeric DNA strand overhang. Recently the crystal structure of this has done just that. Griffith and de Lange show, in this protein complexed with DNA was solved (Horvath et al., issue of Cell, that rather than ending as linear DNA mole-1998). The single-stranded G-rich overhang is com-cules as was previously thought, telomeres in mamma-pletely protected within the protein core and the 3Ј end lian cells end as large terminal loops (Griffith et al., 1999). is inaccessible, as anticipated from biochemical experi-Following the nomenclature of three-stranded DNA dis-they call these new structures " t loops " for telomere loops. The long stretches of the double-stranded telo-mere DNA are looped around, and the single-stranded terminus is tucked back inside the double-stranded DNA molecule—thus protecting the chromosome terminus (Figure 1). These results force us to rethink the classical view of telomere structure and function developed over the past 20 years and provide a context for a new synthesis. The Classical View Telomere Structure. Telomere structure is conserved in almost all eukaryotes. The DNA sequence at telomeres typically consists of tandem GT-rich repeats: (TTGGG G)n in Tetrahymena, (TTTTGGGG)n in a distantly related ciliate, Oxytricha, and (TTAGGG)n in human and mouse. After the initial identification of the simple sequence repeats at telomeres in Tetrahymena (Blackburn and Gall, 1978), Klobutcher et al. showed that in Oxytricha, the G strand is longer than the C strand, indicating a G strand 3Ј end overhang at telomeres (Klobutcher et al., 1981). This provided the first evidence for the end structure that is conserved in all species examined to date. The size of the overhang is species specific, varying from an exact length of 16 nucleotides in Oxytricha to a variable stretch of 50–100 nucleotides in mouse and human telomeres. The fact that mutants that disrupt the G strand overhang also disrupt telomere function suggests that this overhang …