Is there a link between telomere maintenance and radiosensitivity?
Several recent studies point to the possibility that telomere maintenance may constitute a potential genetic marker of radiosensitivity. For example, the human diseases ataxia telangiectasia and Nijmegen breakage syndrome, which are characterized by clinical radiosensitivity, show alterations in telomere maintenance. In addition, Fanconi's anemia patients, who are characterized by mild cellular radiosensitivity and in some cases marked clinical radiosensitivity, have altered telomere maintenance. Similarly, a correlation between telomere maintenance and cellular radiosensitivity was reported in a group of breast cancer patients. Another study demonstrated that radiosensitivity may be more pronounced in human fibroblasts with short telomeres than in their counterparts with long telomeres. Several mouse models including mice deficient in Ku, DNA-PKcs (Prkdc), Parp and Atm, all of which are radiosensitive in vivo, show clear telomere alterations. The link between telomere maintenance and radiosensitivity is also apparent in mice genetically engineered to have dysfunctional telomeres. Finally, studies using non-mammalian model systems such as C. elegans and yeast point to the link between radiosensitivity and telomere maintenance. These results warrant further investigation to identify the extent to which these two phenotypes, namely radiosensitivity and telomere maintenance, are linked.
Slijepcevic
Predrag
P
Brunel Institute of Cancer Genetics & Pharmacogenomics, Brunel University, Kingston Lane, Uxbridge, Middlesex, UB8 3PH, United Kingdom. Predrag.Slijepcevic@brunel.ac.uk
D000818:Animals; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000502:physiology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000235:genetics* / Q000528:radiation effects*; D006801:Humans; D051379:Mice; D010641:Phenotype; D011836:Radiation Tolerance / Q000235:genetics* / Q000502:physiology; D016615:Telomere / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects*