APE1 deficiency promotes cellular senescence and premature aging features

Nucleic Acids Research
Mengxia LiDavid M Wilson

Abstract

Base excision repair (BER) handles many forms of endogenous DNA damage, and apurinic/apyrimidinic endonuclease 1 (APE1) is central to this process. Deletion of both alleles of APE1 (a.k.a. Apex1) in mice leads to embryonic lethality, and deficiency in cells can promote cell death. Unlike most other BER proteins, APE1 expression is inversely correlated with cellular senescence in primary human fibroblasts. Depletion of APE1 via shRNA induced senescence in normal human BJ fibroblasts, a phenotype that was not seen in counterpart cells expressing telomerase. APE1 knock-down in primary fibroblasts resulted in global DNA damage accumulation, and the induction of p16INK4a and p21WAF1 stress response pathways; the DNA damage response, as assessed by γ-H2AX, was particularly pronounced at telomeres. Conditional knock-out of Apex1 in mice at post-natal day 7/12 resulted in impaired growth, reduced organ size, and increased cellular senescence. The effect of Apex1 deletion at post-natal week 6 was less obvious, other than cellular senescence, until ∼8-months of age, when premature aging characteristics, such as hair loss and impaired wound healing, were seen. Low APE1 expression in patient cancer tissue also correlated with increased sen...Continue Reading

References

Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·S XanthoudakisT Curran
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·R FeilP Chambon
Dec 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·D M Wilson, L H Thompson
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·H AtamnaB N Ames
Oct 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·A KrtolicaJ Campisi
Oct 31, 2001·Trends in Cell Biology·J Campisi
May 10, 2002·Nucleic Acids Research·Richard M Cawthon
Jul 13, 2002·Trends in Biochemical Sciences·Thomas von Zglinicki
Mar 22, 2003·RNA·Sheila A StewartCarl D Novina
May 14, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·William C Hahn
Apr 28, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Mark D Evans, Marcus S Cooke
Mar 1, 2005·Cell·David B LombardFrederick W Alt
Aug 2, 2007·Nature Reviews. Molecular Cell Biology·Judith Campisi, Fabrizio d'Adda di Fagagna
Oct 5, 2007·Nucleic Acids Research·Vera GorbunovaChristpher Hine
Jun 3, 2008·Free Radical Biology & Medicine·Meng-Xia LiYi Qing
Mar 20, 2010·Current Aging Science·Fabio Coppedè, Lucia Migliore
Jun 8, 2010·Breast Cancer Research : BCR·Feridoun Karimi-BusheriMichael Weinfeld
Feb 16, 2011·The Journal of Cell Biology·Francis Rodier, Judith Campisi
Nov 30, 2011·Current Molecular Pharmacology·Yun-Jeong Kim, David M Wilson
Nov 13, 2012·Annual Review of Physiology·Judith Campisi
Jul 10, 2013·Antioxidants & Redox Signaling·Mengxia Li, David M Wilson
Oct 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sibylle MadlenerNurten Saydam
Apr 8, 2014·Journal of Molecular Biology·Mengxia LiDavid M Wilson
Aug 12, 2014·Current Opinion in Genetics & Development·Francesca RossielloFabrizio d'Adda di Fagagna
Oct 31, 2014·Carcinogenesis·Boris M BrenermanDavid M Wilson
Nov 2, 2015·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Ana P MontaldiElza T Sakamoto-Hojo
Apr 23, 2017·Mechanisms of Ageing and Development·Kedar N PrasadStephen C Bondy
Jun 3, 2017·Cell·Shenghui He, Norman E Sharpless
Aug 10, 2017·Nature Reviews. Molecular Cell Biology·Nard Kubben, Tom Misteli

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Citations

Dec 19, 2019·International Journal of Molecular Sciences·Duckgue LeeJaeseok Han
Nov 6, 2020·Drug Discovery Today·Rachel A CastonMark R Kelley
Feb 3, 2021·DNA Repair·Alexandra M D'Amico, Karen M Vasquez
Aug 3, 2019·American Journal of Human Genetics·Vinod Tiwari, David M Wilson
Jul 3, 2021·International Journal of Molecular Sciences·Heling WangEvandro F Fang

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Datasets Mentioned

BETA
GM05565
GM00969
J00179

Methods Mentioned

BETA
genotyping
PCR
protein assay
X-ray
flow cytometry
confocal microscopy
immunoprecipitation
gene knock-out

Software Mentioned

LAS X
[UNK] TL
SPSS

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