Mechanisms of genome instability in Hutchinson-Gilford progeria
Received date: 31 Aug 2016
Accepted date: 10 Nov 2016
Published date: 28 Feb 2017
Copyright
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.
Key words： HGPS; DDR; DSB repair
Haoyue Zhang , Kan Cao . Mechanisms of genome instability in Hutchinson-Gilford progeria[J]. Frontiers in Biology, 2017 , 12(1) : 49 -62 . DOI: 10.1007/s11515-016-1435-x
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