TY - JOUR
T1 - Protection of internal (TTAGGG)n repeats in Chinese hamster cells by telomeric protein TRF1
AU - Krutilina, Raisa Ivanovna
AU - Smirnova, Alexandra Nikolaevna
AU - Mudrak, Olga Stanislavovna
AU - Pleskach, Nadezhda Mikhailovna
AU - Svetlova, Maria Pavlovna
AU - Oei, Shiao Li
AU - Yau, Peter M.
AU - Bradbury, Edwin Morton
AU - Zalensky, Andrey Olegovich
AU - Tomilin, Nikolai Viktorovich
N1 - Funding Information:
We thank S Smith for her kind gift of plasmids pTetFLNLS and pUHR15-1. This research was supported by the Office of Science (BER), US Department of Energy, Grant No. DE-FG03-01ER63070, by the National Institutes of Health Grant No. 5R01-HD39830-02, by the Deutsche Forschung Gemeinschaft Grant 436 RUS113/126/0, by the Civilian Research and Development Foundation Grant ST-012-0 and the Russian Fund for Basic Research Grants 01-04-49486 and 02-04-49145.
PY - 2003/9/29
Y1 - 2003/9/29
N2 - Chinese hamster cells have large interstitial (TTAGGG) bands (ITs) which are unstable and should be protected by an unknown mechanism. Here, we expressed in Chinese hamster V79 cells green fluorescent protein (GFP)-tagged human TRF1, and found that a major fraction of GFP-TRF1 bound to ITs is diffusionally mobile. This fraction strongly decreases after treatment of cells with wortmannin, a protein kinase inhibitor, and this drug also increases the frequency of chromosome aberrations. Ionizing radiation does not induce detectable translocation of GFP-TRF1 to the sites of random double-strand breaks visualized using antibodies against histone γ-H2AX. TRF1 is known to be eliminated from telomeres by overexpression of tankyrase 1 which induces TRF1 poly(ADP-ribosyl)ation. We transfected V79 cells by plasmid encoding tankyrase 1 and found that the frequency of chromosome rearrangements is increased in these cells independently of their treatment by IR. Taken together, our results suggest that TRF1 is involved in sequence-specific protection of internal nontelomeric (TTAGGG)n repeats.
AB - Chinese hamster cells have large interstitial (TTAGGG) bands (ITs) which are unstable and should be protected by an unknown mechanism. Here, we expressed in Chinese hamster V79 cells green fluorescent protein (GFP)-tagged human TRF1, and found that a major fraction of GFP-TRF1 bound to ITs is diffusionally mobile. This fraction strongly decreases after treatment of cells with wortmannin, a protein kinase inhibitor, and this drug also increases the frequency of chromosome aberrations. Ionizing radiation does not induce detectable translocation of GFP-TRF1 to the sites of random double-strand breaks visualized using antibodies against histone γ-H2AX. TRF1 is known to be eliminated from telomeres by overexpression of tankyrase 1 which induces TRF1 poly(ADP-ribosyl)ation. We transfected V79 cells by plasmid encoding tankyrase 1 and found that the frequency of chromosome rearrangements is increased in these cells independently of their treatment by IR. Taken together, our results suggest that TRF1 is involved in sequence-specific protection of internal nontelomeric (TTAGGG)n repeats.
KW - Instability
KW - Internal telomeric repeats
KW - TRF1
KW - Tankyrase 1
KW - Wortmannin
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U2 - 10.1038/sj.onc.1206745
DO - 10.1038/sj.onc.1206745
M3 - Article
C2 - 14555982
AN - SCOPUS:0242606276
SN - 0950-9232
VL - 22
SP - 6690
EP - 6698
JO - Oncogene
JF - Oncogene
IS - 42 REV. ISS. 4
ER -