Telomeres and Fanconi's anemia

Fanconi's anemia (FA) is a genetic disease characterized by increased chromosome instability associated with congenital malformations, progressive pancytopenia and increased susceptibility to cancer. FA lymphocytes have an accelerated shortening of telomeres, but the molecular mechanisms involved are unclear. In February Human Molecular Genetics, Elsa Callén and colleagues from Vall d'Hebron Hospital, Barcelona, Spain, show that both telomere breakage and replicative shortening account for the in vivo telomere shortening seen in FA peripheral lymphocytes.

Callén et al. observed an increased telomeric sequence breakage rate leading to the development of extra-chromosomic TTAGGG signals in blood lymphocyte metaphases. Consistent with impaired telomeres, they also found an increase in chromosome end fusions in FA cells. In addition, they observed that the increase in end fusions is independent of the TTAGGG repeat factor 2, TRF2 (Hum Mol Gen 2002, 11:439-444).

These results give new insights into the mechanisms and biological consequences of telomere erosion in ...