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Premature aging syndromes often result from mutations in nuclear proteins involved in the maintenance ofgenomic integrity.Lamin A is a major component of the nuclear lamina and nuclear skeleton.Truncation in lamin A causes Hutchinson-Gilford Progerial Syndrome (HGPS),a severe form of early onset premature aging.Lack of functional ZMPSTE 24,a metall oproteinase responsible for the maturation of prelamin A,also results in progerial phenotypes in mice and humans.We found that Zmpste 24 deficient murine embryonic fibroblasts (MEFs) and fibroblasts from HGPS patients exhibit increased DNA damage and chromosome aberrations and are more sensitive to DNA-damaging agents.Recruitment of check point response proteins and repair proteins to sites of DNA lesions is impaired in Zmpste24-/-cells and HGPS fibroblasts,resulting in defective DNA repair.