Fig. 5.

Pathogenesis of human RECQ helicase deficiency syndromes. A model is depicted that summarizes cellular and organismal consequences of loss of RECQ helicase function during and after development. Heritable loss of RECQ function leads to altered DNA metabolism in most or all cell lineages during and after development. Altered or aberrant DNA metabolism, in turn, leads to genetic instability, epigenetic ‘drift’ and cell loss or senescence that over time may compromise tissue structure and function while promoting the emergence of cells with a proliferative advantage to form specific neoplasms (upper right). Tumor generation is strongest in BS. Loss of WRN function also strongly promotes cellular senescence that contributes to global progeroid changes and may provide a non-specific tumor suppressive mechanism that limits tumor formation to a few susceptible cell lineages such as osteoblasts.