DNA repair in neural cells: basic science and clinical implications.

As one part of a distinguished scientific career, Dr. Bryn Bridges focused his attention on the issue of DNA damage and repair in stationary phase bacteria. His work in this area led to his interest in DNA repair and mutagenesis in another non-dividing cell population, the neurons in the mammalian nervous system. He has specifically taken an interest in the magnocellular neurons of the central nervous system, and the possibility that somatic mutations may be occurring in these neurons. As part of this special issue dedicated to Bryn Bridges upon his retirement, I will discuss the various DNA repair pathways known to be active in the nervous system. The importance of DNA repair to the nervous system is most graphically illustrated by the neurological abnormalities observed in patients with hereditary diseases associated with defects in DNA repair. I will consider the mechanisms underlying the neurological abnormalities observed in patients with four of these diseases: xeroderma pigmentosum (XP), Cockayne's syndrome (CS), ataxia telangectasia (AT) and AT-like disorder (ATLD). I will also propose a mechanism for one of the observations indicating that somatic mutation can occur in the magnocellular neurons of the aging rat brain. Finally, as a parallel to Bridges inquiry into how much DNA synthesis is going on in stationary phase bacteria, I will address the question of how much DNA synthesis in going on in neurons, and the implications of the answer to this question for recent studies of neurogenesis in adult mammals.