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Poly(ADP-ribose) Polymerase Can Bind Melphalan Damaged DNA¹

Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2 [J. B., J. P., A. M., A. J. N., M. A-J., L. P.], and Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier de L'Université Laval, Québec, Québec, Canada G1V 4G2 [G. G. P., S. D.]

As a means of identifying damage recognition proteins involved in repair of nitrogen mustard lesions in chronic lymphocytic leukemia, we performed Southwestern analysis using a probe damaged with melphalan and protein extracts from chronic lymphocytic leukemia patients. We detected proteins with molecular weights of 116,000, 66,000, and 64,000 which bound the damaged probe with a higher specificity than the undamaged probe. The M_r 66,000 and 64,000 proteins were determined to be degradation products of the M_r 116,000 protein. The M_r 116,000 protein was identified as poly(ADP-ribose) polymerase. The use of methoxyamine, an inhibitor of DNA strand breakage following depurination, significantly reduced binding of the melphalan damaged probe to poly(ADP-ribose) polymerase. Following depletion of poly(ADP-ribose) polymerase from the cell extracts, no other binding activity was discovered. Thus, poly(ADP-ribose) polymerase is the only demonstrable protein in chronic lymphocytic leukemia cells which can bind to a DNA probe damaged with melphalan.

¹ Supported by a grant from the Martinex fund, a private donation from Evelyn Steinberg Alexander, and partially from the Cancer Research Society, Montreal, Quebec, Canada.

² To whom requests for reprints should be addressed.

Received 8/ 5/93. Accepted 10/ 4/93.

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