SV40 large T-antigen disturbs the formation of nuclear DNA-repair foci containing MRE11

Martin Digweed, Ilja Demuth, Susanne Rothe, Regina Scholz, Andreas Jordan, Carsten Grötzinger, Detlev Schindler, Markus Grompe, Karl Sperling

Research output: Contribution to journalReview articlepeer-review

58 Scopus citations


The accumulation of DNA repair proteins at the sites of DNA damage can be visualized in mutagenized cells at the single cell level as discrete nuclear foci by immunofluorescent staining. Formation of nuclear foci in irradiated human fibroblasts, as detected by antibodies directed against the DNA repair protein MRE11, is significantly disturbed by the presence of the viral oncogene, SV40 large T-antigen. The attenuation of foci formation was found in both T-antigen immortalized cells and in cells transiently expressing T-antigen, indicating that it is not attributable to secondary mutations but to T-antigen expression itself. ATM-mediated nibrin phosphorylation was not altered, thus the disturbance of MRE11 foci formation by T-antigen is independent of this event. The decrease in MRE11 foci was particularly pronounced in T-antigen immortalized cells from the Fanconi anaemia complementation group FA-D2. FA-D2 cells produce essentially no MRE11 DNA repair foci after ionizing irradiation and have a significantly increased cellular radiosensitivity at low radiation doses. The gene mutated in FA-D2 cells, FANCD2, codes for a protein which also locates to nuclear foci and may, therefore, be involved in MRE11 foci formation, at least in T-antigen immortalized cells. This finding possibly links Fanconi anaemia proteins to the frequently reported increased sensitivity of Fanconi anaemia cells to transformation by SV40. From a practical stand point these findings are particularly relevant to the many studies on DNA repair which exploit the advantages of SV40 immortalized cell lines. The interference of T-antigen with DNA repair processes, as demonstrated here, should be borne in mind when interpreting such studies.

Original languageEnglish (US)
Pages (from-to)4873-4878
Number of pages6
Issue number32
StatePublished - 2002


  • Fanconi anaemia
  • Immortalization
  • Ionizing irradiation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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