An interesting finding by M. A. Blasco et al. was published in Nature, where it was shown that telomere endings were controlled by Rb family proteins.
As the molecular mechanisms of cellular mortality have recently begun to be unraveled, it has been discovered that cells that lack telomerase are subject to telomere attrition with each round of replication, eventually leading to loss of telomere capping function at chromosome ends.
As it is known that critically short telomeres and telomeres lacking telomere-binding proteins lose their functionality and are metabolized as DNA breaks, thus generating chromosomal fusions, so telomerase activity is sufficient to rescue short telomeres and confer an unlimited proliferative capacity.
In addition, the tumor-suppressor pathway Cdkn2a/Rb1 has also been implicated as a barrier to immortalization.
Here, the connection between the members of the retinoblastoma family of proteins, Rb1 (retinoblastoma 1), Rbl1 (retinoblastoma-like 1) and Rbl2 (retinoblastoma-like 2), and the mechanisms that regulate telomere length was reported.
In particular, mouse embryonic fibroblasts doubly deficient in Rbl1 and Rbl2 or triply deficient in Rbl1, Rbl2 and Rb1 had markedly elongated telomeres compared with those of wild type or Rb1-deficient cells.
This deregulation of telomere length was not associated with increased telomerase activity.
Notably, the abnormally elongated telomeres in doubly or triply deficient cells retained their end-capping function, as was shown by the normal frequency of chromosomal fusions.
These findings demonstrated a connection between the Rb1 family and the control of telomere length in mammalian cells.