BLM

The BLM gene provides instructions for making a member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division and for repairing damaged DNA. Because RecQ helicases maintain the structure and integrity of DNA, they are known as the "caretakers of the genome."

When a cell prepares to divide to form two cells, the DNA that makes up the chromosomes is copied so that each new cell will get a complete set of chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. Sister chromatids exchange small sections of DNA (sister chromatid exchange) during this time.

The BLM protein interacts with several other proteins involved in the maintenance of genome integrity. With the help of its partner proteins, BLM suppresses sister chromatid exchanges and helps to maintain the stability of the DNA during the copying process. Researchers believe BLM restarts the DNA copying process when it stalls, an event that probably happens frequently in the cell. In the absence of BLM activity, DNA copying restarts through a mechanism called homologous recombination that results in sister chromatid exchange.

Bloom syndrome - caused by mutations in the BLM gene

More than 70 BLM gene mutations have been identified in people with Bloom syndrome. One particular mutation causes almost all cases of Bloom syndrome among people of Central and Eastern European (Ashkenazi) Jewish descent. This mutation deletes six DNA building blocks (nucleotides) and replaces them with seven others at position 2281 (written as 2281 delta 6ins7, or blmAsh). The blmAsh mutation results in the production of an abnormally short, nonfunctional version of the BLM protein. Other BLM gene mutations change single protein building blocks (amino acids) in the protein sequence or create a premature stop signal in the instructions for making the protein.

Mutations in the BLM gene prevent the protein from performing its function in maintaining genome stability. As a result of the altered BLM protein activity, the frequency of sister chromatid exchange increases about 10-fold, which is a hallmark of Bloom syndrome. Increased sister chromatid exchange is an indicator of chromosome instability. It is associated with gaps and breaks in the genetic material that impair normal cell activities and cause the health problems associated with this condition. Cancer results from genetic changes that allow cells to divide in an uncontrolled way. Altered BLM protein activity may also lead to an increase in cell death, resulting in slow growth in affected individuals.