Werner syndrome is caused by mutations in a specific gene known as the WRN gene. This gene is responsible for producing a protein called Werner syndrome helicase, which plays a crucial role in maintaining the stability and integrity of our DNA. The WRN protein belongs to a family of enzymes called RecQ helicases, which are essential for repairing damaged DNA and ensuring that cells can replicate their DNA correctly during cell division.
When the WRN gene is mutated, the resulting protein either does not function properly or is not produced at all. This loss of function impairs the cell’s ability to repair DNA damage, particularly DNA double-strand breaks, which are among the most severe types of genetic damage. Without effective repair, DNA accumulates errors and becomes unstable, leading to genomic instability. This instability causes cells to age prematurely, stop dividing, or die, which is why Werner syndrome is classified as a premature aging disorder.
The defective WRN helicase disrupts several critical cellular processes:
– **DNA repair:** Normally, WRN helps unwind DNA strands to allow repair enzymes to access and fix breaks or errors. Mutations hinder this process, leading to persistent DNA damage.
– **DNA replication:** WRN assists in the smooth copying of DNA during cell division. Its absence causes replication stress, increasing the chance of mutations.
– **Telomere maintenance:** Telomeres are protective caps at the ends of chromosomes that shorten with age. WRN helps maintain telomere length, and its dysfunction accelerates telomere shortening, contributing to cellular aging.
Because DNA damage accumulates and cells lose their ability to divide properly, tissues and organs begin to show signs of early aging. This manifests as symptoms such as graying hair, skin changes, cataracts, osteoporosis, and an increased risk of age-related diseases like cancer and cardiovascular problems.
In summary, Werner syndrome arises from inherited mutations in the WRN gene that impair the function of the WRN helicase protein. This impairment leads to defective DNA repair and genomic instability, causing cells to age prematurely and resulting in the characteristic features of this rare genetic disorder.
