[Frontiers in Bioscience 10, 1779-1796, May 1, 2005]

EPIGENETIC CONTROL OF TELOMERASE AND MODES OF TELOMERE MAINTENANCE IN AGING AND ABNORMAL SYSTEMS

Serene R. Lai 1, Sharla M. O. Phipps 1, Liang Liu 1, Lucy G. Andrews 1 and Trygve O. Tollefsbol 1, 2, 3

1 Department of Biology, University of Alabama at Birmingham, AL 35294, USA, 2 Center of Aging, University of Alabama at Birmingham, AL 35294, USA, 3 Comprehensive Cancer Center, University of Alabama at Birmingham, AL 35294, USA

FIGURES

Figure 1. p21, cdk2, cyclin E, pRB, and E2F interaction and the resulting effects on the cell cycle. In proliferating cells, phosphorylation of pRB by cdk2-cyclin E complex prevents binding of pRB to E2F, thus enabling E2F to be involved in the transcription of S-phase related proteins. In differentiated or senescent cells, p21 can act as a CDKI to prevent the downstream phosphorylation of pRB, allowing pRB to sequester E2F, and eventually preventing the entry of the cell into S-phase.

Figure 2. Interlinked pathways involving cell cycle proteins p53 and p21, c-Myc, and potential epigenetic control on hTERT, the telomerase catalytic subunit. Positive regulation is represented by solid arrows, while negative regulation is represented by dashed-arrows.

Figure 3. Depiction of telomere binding proteins and proteins affecting telomerase recruitment to telomeres. (A) Negative regulation of telomere extension via feedback loop by TRF1-POT1 complex, with T-loop stabilization by TRF2 and POT1. TRF2-hRap1 complex prevents telomerase access to the terminal 3' end. (B) Positive regulation of telomere extension via tankyrase ADP-ribosylating function to remove TRF1 from the telomeres. hEST1A recruits telomerase holoenzyme by binding to hTERT.