Conservation of telomere protein complexes: shuffling through evolution

Abstract

The rapid evolution of telomere proteins has hindered identification of orthologs from diverse species and created the impression that certain groups of eukaryotes have largely non-overlapping sets of telomere proteins. However, the recent identification of additional telomere proteins from various model organisms has dispelled this notion by expanding our understanding of the composition, architecture and range of telomere protein complexes present in individual species. It is now apparent that versions of the budding yeast CST complex and mammalian shelterin are present in multiple phyla. While the precise subunit composition and architecture of these complexes vary between species, the general function is often conserved. Despite the overall conservation of telomere protein complexes, there is still considerable species-specific variation, with some organisms having lost a particular subunit or even an entire complex. In some cases, complex components appear to have migrated between the telomere and the telomerase RNP. Finally, gene duplication has created telomere protein paralogs with novel functions. While one paralog may be part of a conserved telomere protein complex and have the expected function, the other paralog may serve in a completely different aspect of telomere biology.

Figure 1

Telomere cycling between (A) closed and (B) open conformations.

Figure 2

Steps during telomere replication. Adapted from (Price, 2009). Color figure available online.

Figure 3

Organization of telomere protein complexes in (A) S. cerevisiae and (B) Human cells. Color figure available online.

Figure 4

Structural domains of telomeric DNA binding proteins. (A) Ribbon diagram of the Myb domain from human TRF1 bound to ds telomeric DNA. (B) OB-fold 1 (OB1) from human POT1 bound to telomeric G-strand DNA. Purple, telomeric DNA; red, α-helicies; yellow, β-strands; green, loops. (C) Domain structure of POT1 homologs from H. Sapiens, S. pombe and O. nova with % identity shown between OB1, OB2, or the full-length protein. Color figure available online.

Figure 5

Organization of the shelterin complex from S. pombe. Color figure available online.

Figure 6

Model for telomere replication in budding yeast and mammals. (A) Role of CST in S. cerevisiae. Cdc13 recruits telomerase via direct interaction with Est1. Cdc13 and Stn1 interact with subunits of Pol α-primase, recruiting it for C-strand synthesis. (B) Role of shelterin and CST in mammalian cells. TPP1 promotes telomerase action while CST recruits Pol α-primase for C-strand synthesis. Color figure available online.

Figure 7

Functional domains within human TRF1 and TRF2. Arrows indicate percent identity between domains or the full-length proteins. Interactions partners are indicted and regions mediating the interaction are underlined. Color figure available online.