BLM Helicase Maintains Telomeres in the Absence of Telomerase

Joanna Groden, Ph.D.
University of Cincinnati
P30ES006096

Background: Bloom’s syndrome is a rare human genetic disorder characterized by growth delay and short stature, sun-sensitive redness of facial skin, increased respiratory tract and ear infections, and a risk of cancer as much as 150­300 times higher than the general population. Dr. David Bloom, a New York dermatologist, first described the condition in 1954. The gene mutation is very rare in most populations, but is more frequent in Ashkenazi Jews, where the carrier rate is about 1%. The malignancies that are associated with Bloom’s syndrome are varied and include acute leukemia, lymphoma, and cancers of the gastrointestinal tract. BLM, the gene mutated in Bloom’s syndrome, encodes an enzyme called RecQL3 helicase. This family of helicases unwinds DNA so that replication, transcription, and DNA repair can occur properly. Individuals with Bloom’s syndrome have an unusually high number of chromosomal breaks and rearrangements.

Recent research has shown that BLM is associated with a phenomenon called alternative lengthening of telomeres. Telomeres are the caps on the ends of chromosomes. In normal conditions, telomeres shorten each time a cell divides, eventually exposing the genetic material and causing the cell to die. In cancer cells, however, an enzyme known as telomerase keeps rebuilding the telomere caps, preventing the cell from undergoing its normal aging process. Studies have suggested that BLM promotes alternative lengthening of telomeres.

Advance: New research by this NIEHS­supported researcher at the University of Cincinnati shows that expression of BLM maintains telomere lengthening in a transgenic yeast model lacking telomerase. The helicase produced from expression of the gene is responsible for maintaining the telomere lengths and presumably interferes with the normal cellular aging process.

Implications: The authors of the study point out that the exact mechanisms by which the telomere lengthening occurs and the role the helicase plays in these pathways are still unknown. The study does show that BLM is an important component in maintaining telomeres and sheds light on the cellular mechanisms leading to Bloom’s syndrome.

Citation: Lillard­etherell K, Combs KA, Groden J. BLM helicase complements disrupted type II telomere lengthening in telomerase-negative sgs1 yeast. Cancer Res. 2005 Jul 1;65(13):5520-2.