BS is caused by mutations in the BLM gene, which encodes for the Bloom syndrome protein, a RecQ helicase. These mutations may be frameshift, missense, non-sense, or mutations of other kinds and are likely to cause deletions in the gene product. Apart from helicase activity that is common to all RecQ helices, it also acts to prevent inappropriate homologous recombination. During replication of the genome, the two copies of DNA, called sister chromatids, are held together through a structure called the centromere. During this time, the homologous (corresponding) copies are in close physical proximity to each other, allowing them to 'cross' and exchange genetic information, a process called homologous recombination. Defective homologous recombination can cause mutation and genetic instability. Such defective recombination can introduce gaps and breaks within the genome and disrupt the function of genes, possibly causing growth retardation, aging and elevated risk of cancer. It introduces gaps and breaks within the genome and disrupts the function of genes, often causing retardation of growth, aging and elevated risks of cancers. The Bloom syndrome protein interacts with other proteins, such as topoisomerase IIIα and RMI2, and suppresses illegitimate recombination events between sequences that are divergent from strict homology, thus maintaining genome stability. Individuals with BS have a loss-of-function mutation, which means that the illegitimate recombination is no longer suppressed, leading to higher rates of mutation (~10-100 times above normal, depending on cell type).
