Molecular and biochemical aspects of Bloom's syndrome

Bloom's syndrome (BS) is an autosomal recessive disorder, characterized by a high incidence of cancer at a young age. Cytogenetically, BS cells exhibit a high frequency of chromosomal damage and sister chromatid exchanges. Thus, BS provides one of the best correlations of a human genetic disorder exhibiting both chromosomal instability and a high incidence of cancer. It is increasingly evident that a spontaneous mutagenic event may be responsible for the inherent chromosomal instability. Oxidative stress is now shown to occur in BS cells and may be responsible for the observed chromosomal instability. Furthermore, treatment with antioxidants decreases the level of sister chromatid exchanges. The combination of a mutagenic event and an elevated rate of recombination could potentially lead to homozygosity of tumor suppressor gene function. Hypomethylation and expression of an activated c-myc gene are now demonstrated in BS lymphoblastoid cells. Identifying the mechanism(s) of the ongoing cellular and DNA damage is important in understanding the etiology of this complex disorder. This article reviews the recent biochemical and molecular advances in the study of BS.