ABSTRACT
Bloom’s syndrome differs in that affected individuals exhibit apparently normal unscheduled DNA synthesis but show significant sister chromatid exchange, suggesting that this autosomal recessive disorder may exhibit a functional but aberrant form of excision repair. Since elevated levels of the occurrence of a variety of cancer types are a characteristic of increased age, investigators have speculated that dysfunction of DNA excision repair may be age related. In the studies of human DNA polymerase alpha presented here, the enzyme isolated from fetal-derived cells has been characterized as stable, highly active, and having a high affinity of binding to DNA template/primer, while enzyme isolated from adult-derived fibroblasts has two forms (putative isozymes). Examinations of cultured cells have shown an approximate twofold increase in accumulation of mutations during the initial two thirds of the in vitro cell life span, with a rapid accumulation of mutations during the latter part of the life span.
