Telomere Sister Chromatid Exchange in Telomerase Deficient Murine Cells

We have recently demonstrated that several types of genomic rearrangements (i.e. telomere sister chromatid exchange (T-SCE), genomic-SCE, or end-to-end fusions) were more often detected in long-term cultured murine telomerase deficient embryonic stem (ES) cells than in freshly prepared murine splenocytes, even through they possessed similar frequencies of critically short telomeres. The high rate of genomic rearrangements in telomerase deficient ES cells, when compared to murine splenocytes, may reflect the cultured cells’ gained ability to protect chromosome ends with eroded telomeres allowing them to escape “end crisis”. However, the possibility that ES cells were more permissive to genomic rearrangements than other cell types or that differences in the microenvironment or genetic background of the animals might consequentially determine the rate of T-SCEs or other genomic rearrangements at critically short telomeres could not be ruled out.

[1]  G. Wahl,et al.  The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Richard J. Giannone,et al.  An increase in telomere sister chromatid exchange in murine embryonic stem cells possessing critically shortened telomeres. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Klatt,et al.  Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs , 2004, The Journal of cell biology.

[4]  Margaret A. Strong,et al.  Phosphorylation of H2AX at Short Telomeres in T Cells and Fibroblasts* , 2004, Journal of Biological Chemistry.

[5]  M. Kastan,et al.  The Telomeric Protein TRF2 Binds the ATM Kinase and Can Inhibit the ATM-Dependent DNA Damage Response , 2004, PLoS biology.

[6]  M. Brenneman,et al.  Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells. , 2004, Nucleic acids research.

[7]  J. Shay,et al.  Telomeric Recombination in Mismatch Repair Deficient Human Colon Cancer Cells after Telomerase Inhibition , 2004, Cancer Research.

[8]  S. West,et al.  Telomere Maintenance Requires the RAD51D Recombination/Repair Protein , 2004, Cell.

[9]  Yie Liu,et al.  Distinct dosage requirements for the maintenance of long and short telomeres in mTert heterozygous mice. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Carter,et al.  A DNA damage checkpoint response in telomere-initiated senescence , 2003, Nature.

[11]  T. Lange,et al.  DNA Damage Foci at Dysfunctional Telomeres , 2003, Current Biology.

[12]  R. Reddel.  Alternative lengthening of telomeres, telomerase, and cancer. , 2003, Cancer letters.

[13]  M. Blasco,et al.  Functional interaction between DNA‐PKcs and telomerase in telomere length maintenance , 2002, The EMBO journal.

[14]  J. Cigudosa,et al.  Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres , 2002, The EMBO journal.

[15]  A. Smogorzewska,et al.  Senescence Induced by Altered Telomere State, Not Telomere Loss , 2002, Science.

[16]  M. Ungrin,et al.  Preferential maintenance of critically short telomeres in mammalian cells heterozygous for mTert , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Hande,et al.  The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo , 2000, Current Biology.

[18]  J. Soria,et al.  [Telomeres, telomerase and cancer]. , 1997, Bulletin du cancer.

[19]  H. Tanke,et al.  Telomeres in the mouse have large inter-chromosomal variations in the number of T2AG3 repeats. , 1997, Proceedings of the National Academy of Sciences of the United States of America.