What are the observations regarding telomere integrity and function in Fanconi anemia?
In Fanconi anemia patients, a higher rate of breakage at TTAGGG sequences in vivo is causing telomere erosion in differentiated cells. Moreover, it has been demonstrated that αIISp is important for telomere maintenance after DNA damage due to interstrand cross-links (ICL), localizing to telomeres in S phase after ICL damage where it has enhanced association with TRF1 and TRF2 and is required for recruitment of the ICL repair protein, XPF, to damage-induced foci at telomeres. In telomerase-positive normal cells depleted of αIISp by siRNA or in Fanconi anemia, complementation group A (FANCA) cells, where αIISp levels are 35-40% of normal, ICL damage results in failure of XPF to localize to telomeres, with markedly increased telomere dysfunction-induced foci, and catastrophic loss of telomeres.