BACKGROUND:Hutchinson-Gilford progeria syndrome (HGPS) is a devastating premature aging disorder.It arises from a single point mutation in the LMNA gene.This mutation stimulates an aberrant splicing event and produces progerin,an isoform of the lamin A protein.Accumulation of progerin disrupts numerous physiological pathways and induces defects in nuclear architecture,gene expression,histone modification,cell cycle regulation,mitochondrial functionality,genome integrity and much more.OBJECTIVE:Among these phenotypes,genomic instability is tightly associated with physiological aging and considered a main contributor to the premature aging phenotypes.However,our understanding of the underlying molecular mechanisms of progerin-caused genome instability is far from clear.RESULTS AND CONCLUSION:In this review,we summarize some of the recent findings and discuss potential mechanisms through which,progerin affects DNA damage repair and leads to genome integrity.