Figure 5. The fold-back may contribute to telomere protection.

The maintenance of telomere structure requires the telomere-bound Rif2 protein to ensure that the Rpd3L complex gets properly loaded/maintained at chromosome ends. The presence of the Rpd3L KDAC (as well as Rpd3S, Sir2 and Hda1) promotes a protective structure at telomeres, which likely eminates in a fold-back of the telomeric DNA onto the subtelomeric region (1.). In the absence of this structure, telomeres remain protected due to a combination of telomerase-mediated elongation and capping via the CST complex (2.). When both capping and the fold-back structure are simultaneously compromised (3.) chromosome ends undergo accelerated nucleolytic degradation, and experience an accelerated rate of senescence in cells lacking a telomere maintenance mechanism due to the fact that rapidly resected uncapped telomeres do not get re-elongated.