Telomeres interact with numerous proteins, including components of the shelterin 
complex, whose alteration, similarly to proliferation-induced telomere 
shortening, initiates cellular senescence. In tumors, telomere length is 
maintained by Telomerase activity or by the Alternative Lengthening of Telomeres 
mechanism, whose hallmark is the telomeric localization of the promyelocytic 
leukemia (PML) protein. Whether PML contributes to telomeres maintenance in 
normal cells is unknown. We show that in normal human fibroblasts the PML 
protein associates with few telomeres, preferentially when they are damaged. 
Proliferation-induced telomere attrition or their damage due to alteration of 
the shelterin complex enhances the telomeric localization of PML, which is 
increased in human T-lymphocytes derived from patients genetically deficient in 
telomerase. In normal fibroblasts, PML depletion induces telomere damage, 
nuclear and chromosomal abnormalities, and senescence. Expression of the 
leukemia protein PML/RARα in hematopoietic progenitors displaces PML from 
telomeres and induces telomere shortening in the bone marrow of pre-leukemic 
mice. Our work provides a novel view of the physiologic function of PML, which 
participates in telomeres surveillance in normal cells. Our data further imply 
that a diminished PML function may contribute to cell senescence, genomic 
instability, and tumorigenesis.