Progerin can induce DNA damage in the absence of global changes in replication or cell proliferation.

Autor: Joudeh LA; Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America., Schuck PL; Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America., Van NM; Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America., DiCintio AJ; Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America., Stewart JA; Department of Biology, Western Kentucky University, Bowling Green, Kentucky, United States of America., Waldman AS; Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Dec 05; Vol. 19 (12), pp. e0315084. Date of Electronic Publication: 2024 Dec 05 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0315084
Abstrakt: Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging, and individuals with HGPS seldom live beyond their mid-teens. The syndrome is commonly caused by a point mutation in the LMNA gene which codes for lamin A and its splice variant lamin C, components of the nuclear lamina. The mutation causing HGPS leads to production of a truncated, farnesylated form of lamin A referred to as "progerin." Progerin is also expressed at low levels in healthy individuals and appears to play a role in normal aging. HGPS is associated with an accumulation of genomic DNA double-strand breaks (DSBs) and alterations in the nature of DSB repair. The source of DSBs in HGPS is often attributed to stalling and subsequent collapse of replication forks in conjunction with faulty recruitment of repair factors to damage sites. In this work, we used a model system involving immortalized human cell lines to investigate progerin-induced genomic damage. Using an immunofluorescence approach to visualize phosphorylated histone H2AX foci which mark sites of genomic damage, we report that cells engineered to express progerin displayed a significant elevation of endogenous damage in the absence of any change in the cell cycle profile or doubling time of cells. Genomic damage was enhanced and persistent in progerin-expressing cells treated with hydroxyurea. Overexpression of wild-type lamin A did not elicit the outcomes associated with progerin expression. Our results show that DNA damage caused by progerin can occur independently from global changes in replication or cell proliferation.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Joudeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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