- B.S., University of Geneva, 1990
- M.A., Princeton University, 1992
- Ph.D., John Hopkins School of Medicine, 1998
- Postdoc, Rockefeller University
Telomere Function in Human Cells
Human chromosome ends (telomeres) are composed of long stretches of TTAGGG repeats and end with a ~150 single stranded overhang. Telomere integrity is essential for chromosome stability and cellular proliferation. As a normal process, telomeres shorten at each cell division until they are too short to sustain growth, at which point cells undergo an irreversible arrest called senescence. Senescence can be completely bypassed by forced expression of telomerase, the enzyme that synthesizes the telomeric repeats, which provides cells with infinite replicative potential.
Proteins that bind to telomeres regulate their length and ensure their protection. A complex of six proteins, named shelterin, is critical for telomere function: TRF1, TRF2, Tin2, Rap1, TPP1 and POT1. In the laboratory, we are studying the role of POT1 at telomeres: this component can regulate the activity of telomerase at chromosome ends. POT1 binds specifically to the telomeric overhang, and this activity is essential for inhibiting telomere elongation in cis. It is the relationship between shelterin, POT1 and telomerase in human cells that constitutes the prime focus of the laboratory.
- J. Ye, D. Hockemeyer, A.N. Krutchinsky, D. Loayza, S.M. Hooper, B.T. Chait, and T. de Lange (2004) POT1 Interacting Protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes and Development 18:1649.
- D. Loayza, H. Parsons, J. Donigian, K. Hoke and T. de Lange (2003) DNA binding features of human POT1. J.Biol.Chem. (2004) 279:13241. [minimal binding site for POT1 binding to single stranded DNA + some DNA binding features].
- D. Loayza and T. de Lange (2003) POT1 as a terminal transducer of TRF1 telomere length control. Nature 423:1013. [deletion of the DNA binding domain of POT1 does not affect recruitment to telomeres but leads to extensive telomere elongation].
- Sheppard, S.A. and D. Loayza (2010) LIM-domain proteins TRIP6 and LPP associate with shelterin to mediate telomere protection.Aging (Albany NY). 2010 Jul 14. [Epub ahead of print]. PMID: 20634563.