Prelamin-A/C

[8] In the setting of ZMPSTE24 deficiency, the final step of lamin processing does not occur, resulting in an accumulation of farnesyl-prelamin A.

Consequently, no mature lamin A is formed, and a farnesylated mutant prelamin A (progerin) accumulates in cells.

Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression.

DNA double-strand damages can be repaired by either homologous recombination (HR) or non-homologous end joining (NHEJ).

LMNA promotes genetic stability by maintaining the levels of proteins that have key roles in HR and NHEJ.

Biogenesis of lamin A in normal cells and the failure to generate mature lamin A in Hutchinson–Gilford progeria syndrome .
Wild type (left) and mutated (right) form of the Ig-fold of lamin A (LMNA, PDB: 1IFR). Normally, arginine 527 (blue) forms a salt bridge with glutamate 537 (magenta), but R527L substitution results in breaking this interaction (leucine is too short to reach glutamate). Models are presented in surface (upper) and in cartoon (lower) representation. [ 11 ]