DNA repair and the molecular mechanisms of Bloom's syndrome.

This critical review considers recent work on alterations in DNA repair capacity in Bloom's syndrome as a molecular mechanism for this human disorder. Four main types of DNA repair deficiencies are discussed. These include perturbations in the temporal regulation of DNA repair pathways during the cell cycle, failure to enhance DNA repair pathways during cell proliferation, reduced levels of DNA ligase in Bloom's syndrome cells, and the identification of mutant repair enzyme proteins. These deficiencies are considered in relation to the cellular characteristics of Bloom's syndrome, including delays in DNA replication, hypermutability, and increased incidence of chromosomal aberrations (spontaneously occurring or observed after exposure to environmental agents). The relationship between DNA repair deficiencies and the genetic basis of Bloom's syndrome is described. Previous evidence suggested an autosomal recessive mode of inheritance for Bloom's syndrome. A discussion is presented as to the molecular mechanism through which an alteration in a single gene could result in multiple DNA repair defects.