ABSTRACT
Genetically determined chromosomal instability was first discovered in Bloom syndrome (BS), a clinical entity that is now known to be the result of mutations in the recQ gene BLM. The RecQ proteins are a large family of evolutionarily conserved DNA helicases, which are enzymes that unwind double-stranded DNA (dsDNA), and they function in ways not completely understood in the maintenance of genomic stability (1). In all biological systems studied so far, mutations in the recQ helicase genes result in various genomic instabilities that are detectable at both the level of the chromosomes and the genomic DNA. In humans, there are five recQ genes, three of which are associated with human diseases, namely BS, Werner syndrome (WS), and Rothmund-Thomson syndrome (RTS). A comparison of the clinical and genetic features of these three syndromes is presented in Table 1. WS results from mutations in the recQ helicase WRN, and it is most remarkable clinically for the development prematurely of features of aging (see Chapter 9). Consequently, WS has served as a model for understanding the aging process.
