Guarding chromosomes from oxidative DNA damage to the very end.
Author: Tan R1, Lan L2
Affiliation:
1Xiangya Hospital, Central South University, Changsha 410008, China University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
2University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA lil64@pitt.edu.
Conference/Journal: Acta Biochim Biophys Sin (Shanghai).
Date published: 2016 May 12
Other:
Word Count: 289
The ends of each chromosome are capped by the telomere assembly to protect chromosomal integrity from telomere attrition and DNA damage. In response to DNA damage, DNA repair factors are enriched at damage sites by a sophisticated signaling and recruitment cascade. However, DNA damage response at telomeres is different from non-telomeric region of genomic DNA due to specialized sequences and structures of the telomeres. In the course of normal DNA replication or DNA damage repair, both the telomere shelterin protein complex and the condensed telomeric chromatin structure in mammalian cells are modified to protect telomeres from exposing free DNA ends which are subject to both telemere shortening and chromosome end fusion. Initiation of either homologous recombination or non-homologous end joint repair at telomeres requires disassembling and/or post-translational modifications of the shelterin complex and telomeric chromatin. In addition, cancer cells utilize distinct mechanisms to maintain telomere length and cell survival upon damage. In this review, we summarize current studies that focus on telomere end protection and telomere DNA repair using different methodologies to model telomere DNA damage and disruption. These include genetic ablation of sheltering proteins, targeting endonuclease to telomeres, and delivering oxidative damage directly. These different approaches, when combined, offer better understanding of the mechanistic differences in DNA damage response between telomeric and genomic DNA, which will provide new hope to identify potential cancer therapeutic targets to curtail cancer cell proliferation via induction of telomere dysfunctions.
© The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
KEYWORDS: KillerRed; oxidative DNA damage; recombination; shelterin; telomere
PMID: 27174872 [PubMed - as supplied by publisher]
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