Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway

Genetically defined mouse cells are utilized to understand the impact of WRN helicase deficiency on telomere maintenance, chromosomal stability, cellular mortality and tumorigenesis. It is indicated that the increased incidence of chromosomal instability and cancer in Werner Syndrome is found due to aberrant recombinations between sister chromatids specifically at telomeres, which promote the activation of the alternative lengthening of telomere (ALT) pathway and lead to chromosomal instability during tumorigenesis.