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Murnane, J.P., Byfield, J.E., Ward, J.F., and Calabro-Jones, P.  Effects of methylated xanthines on mammalian cells treated with bifunctional alkylating agents.  Nature 285:326-329 (1980). 

This manuscript showed that caffeine inhibits DNA damage-induced replicon initiation (now known as the S phase checkpoint), and proposed that the sensitization of cells to DNA damage by caffeine results from of the loss of regulation of DNA synthesis. This was the first study to demonstrate and propose that cell cycle regulation has an important role in protecting cells from DNA damage, and that loss of this regulation can sensitize cells to DNA damage. This study preceded the discovery of a similar deficiency in cell cycle regulation in the human genetic disease ataxia-telangiectasia, and caffeine is now known to work through its inhibition of the ATM protein involved in this disease. I designed the experiments, performed the work, interpreted the results, and wrote the manuscript.

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Murnane, J.P., Sabatier, L., Marder, B. and Morgan, W.F.  Telomere dynamics in an immortal human cell line.  EMBO J. 13:4953-4962 (1994).  

This was the first study to demonstrate that telomeres can be maintained in immortal human cells without telomerase by a mechanism we proposed to involve recombination, now referred to as the ALT pathway. The results also suggested that genomic instability can result from factors influencing telomere loss. I designed the project, performed much of the work, , interpreted the results, and wrote the manuscript.

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Sabatier, L., Ricoul, M., Pottier, G., Mathieu, N. and Murnane, J.P.  The loss of a single telomere can result in instability of multiple chromosomes in a human tumor cell line. Mol. Can. Res., 3:139-150 (2005).

This study demonstrates that the chromosome instability resulting from the loss of a single telomere in a human cancer cell line can be transferred from one chromosome to another, resulting in a variety of chromosome rearrangements commonly found in human cancer. These results point to telomere loss as an important mechanism for both the radiation-induced and spontaneous chromosome instability associated with human cancer. I designed the project and wrote the manuscript.

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Gao, Q, Reynolds, G. E., Wilcox, A., Miller, D., Cheung, P., Artandi, S., and Murnane, J.P.  Telomerase-dependent and independent mechanisms of chromosome healing in mouse embryonic stem cells. DNA Repair, 7:1233-1249 (2008). 

This study used a system developed in the lab to monitor the addition of telomeres to the sites of chromosome breaks (Proc. Natl. Acad. Sci. USA 96:6781-6786, 1999) to demonstrate that chromosome healing in mouse ES cells involves telomerase, although cells that maintain telomeres through an alternative mechanism can also perform chromosome healing. I designed the project, oversaw the work, and wrote much of the manuscript.

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Wilson, C, Murnane, JP. High-throughput screen to identify compounds that prevent or target telomere loss in human cancer cells. Nucleic Acids Res. Cancer, 4:zcac029. (2022).

This manuscript is the latest in a series of reports that follow up on our discoverey that telomeric regions are highly sensitive to DNA double-strand breaks. This sensitivity of subtelomeric regions has now been shown to be important in radiation-induced senescence, and our work shows that it is an important mechanism for telomere loss and chromosome instability in human cancer cells. The current project involves the creation of a high throughput screen to identify compounds that affect telomere loss or selectively target and kill cells experiencing telomere loss due to subtelomeric DSBs introduced by I-SceI endonuclease, as detected by cells expressing green fluorescent protein (GFP). I conceived of the project, constructed the plasmids and cell clone utilized in the project, analyzed the data, and wrote the manuscript.