Journal of The Federation of American Societies for Experimental Biology (FASEB),
May 2001
June 2001
If Patrick's loss has caused us to have to pause and attempt to recover, the researchers are coping differently. They have thrown themselves into the research in a way that can only be described as awe-inspiring.
The scientists clearly have a mission with a face and a name. They are determined to honor Patrick through finding a treatment for A-T. They know that their discoveries will also contribute to a better understanding of cancer and other diseases A-T causes. Driven by these motivations, they work night after day after night, looking for answers.
Not surprisingly, the work of the M. D. Anderson group has resulted in the publication of a milestone scientific paper recently. The article, entitled "The ataxia-telangiectasia gene product may modulate DNA turnover and control cell fate by regulating cellular redox in lymphocytes," (abstract below) appears in the May issue of the very prestigious Journal of The Federation of American Societies of Experimental Biology (FASEB). The information presented in this paper confirms and surpasses a recent publication by the Israeli team that found the A-T gene and will probably prove essential to finding a treatment for children with A-T.
We congratulate Paul Wong, Bill Lynn, and their incredible team for what they have accomplished. We thank each of you for helping us to help them in pursuit of our common quest. Together, we will ultimately prevail.
ABSTRACT:
The ataxia-telangiectasia gene product may modulate DNA turnover and control cell fate by regulating cellular redox in lymphocytes
Journal of The Federation of American Societies for Experimental Biology (FASEB),
May 2001
Mingshan Yan, Wenan Qiang, Na Liu, Jianjun Shen, William S. Lynn And Paul K. Y. Wong
The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division,
Smithville, Texas 78957, USA
Correspondence: The University of Texas M. D. Anderson Cancer Center, Science Park, Research Division, P.O. Box 389, Smithville, TX 78957, USA. E-mail: pwong@sprd1.mdacc.tmc.edu
"The ATM kinase, when activated postnatally, exerts multiple functions to prevent the onset of ataxia-telangiectasia (AT). Using freshly isolated thymocytes from Atm-/- mice that were under stress during postnatal differentiation, we noted that thiol redox activity, as indicated by reduction of the tetrazolium MTS, and DNA turnover activity, as indicated by incorporation of [3H]thymidine into DNA, were both greatly increased compared with activities in thymocytes from Atm+/+ mice. This increased thymidine incorporation could be suppressed by the thiol N-acetylcysteine. In primary noncycling splenocytes, mitogens proportionally increased both the rate of [3H]thymidine incorporation and the rate of reduction of MTS. The mitogen-induced activities in splenocytes were not affected by ATM but were suppressed by the calcineurin-dependent inhibitor FK-506, which has no effect on these activities in thymocytes. These findings suggest that increased [3H]thymidine incorporation and reducing power indicate increased cell cycling in mitogenically stimulated splenocytes, whereas these two indicators represent increased FK-506-independent DNA turnover activities in thymocytes. Thus, a primary function of ATM is to activate the redox-sensitive checkpoint required for down-regulation of DNA turnover activities in developing lymphocytes. Cell-cycling checkpoints in undamaged quiescent lymphocytes are not activated by ATM with mitogenic stimulation. ATM may suppress abnormal DNA turnover and the resultant oncogenesis by regulating cellular thiol redox pathways."