The Lamins are Major Determinants of Nuclear Architecture

The A‐and B‐type nuclear lamins (LA/C, LB1 and LB2) form separate but interconnecting networks within the nuclear lamina and nucleoplasm. Hundreds of mutations in the LMNA gene cause a wide range of diseases including the premature aging disease, Hutchinson‐Gilford Progeria Syndrome (HGPS). The nuclei of HGPS patients’ cells exhibit a wide range of changes in the architecture of their nuclei, including the formation of LA/C rich nuclear envelope blebs, a loss of peripheral heterochromatin, alterations in epigenetic modifications of chromatin, and changes in the RNA pol II transcriptional machinery. Recently we have focused our attention on the mechanisms responsible for the premature senescenece of cells derived from HGPS patients. The results demonstrate that the nuclear lamins are critical factors in the proliferation and senescence of both normal diploid and HGPS cells. Supported by the NCI and the Progeria Research Foundation.