Abo Bibliothek: Guest
Digitales Portal Digitale Bibliothek eBooks Zeitschriften Referenzen und Berichte Forschungssammlungen
Critical Reviews™ in Eukaryotic Gene Expression
Impact-faktor: 2.156 5-jähriger Impact-Faktor: 2.255 SJR: 0.649 SNIP: 0.599 CiteScore™: 3

ISSN Druckformat: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v21.i4.30
pages 323-336

Replication of Damaged Genomes

Alden C. Klarer
Department of Biochemistry and Molecular Biology, University of Louisville; James Graham Brown Cancer Center, University of Louisville
W. Glenn McGregor
University of Louisville


Cellular DNA is continuously assaulted by chemical and physical agents that arise from both endogenous metabolic processes as well as exogenous insults. Commonly encountered environmental agents include polyaromatic hydrocarbons, polycyclic aromatic amines, the ultraviolet component of sunlight, and ionizing radiation, among many others. Although the kinds of damages and the mechanisms involved in their interaction with DNA vary widely, genotoxic agents alter the structure of DNA in ways that may result in permanent alterations in the DNA sequence or in cell death. To avoid these consequences, cells have evolved countermeasures to reduce the biological consequences of DNA damage. These mechanisms are highly conserved and are present in all eukaryotic cells. In general, cellular responses include the detection of damage, signal transduction to halt cell cycle progression, and the recruitment of repair mechanisms that are tailored to the specific kind of damage. If replication-blocking damage remains when cells enter S-phase, then tolerance mechanisms in the form of complex recombination mechanisms or translesion DNA synthesis using accessory DNA polymerases exist. These mechanisms complete the replication of damaged genomes and suppress cytotoxicity, but at the potential cost of mutagenesis and genomic instability. This review focuses on error-prone mechanisms, including a discussion of the Y-family of DNA polymerases, current concepts of DNA polymerase switching mechanisms, and their relevance to cancer and cancer prevention.

Articles with similar content:

The Contribution of DNA Base Damage to Human Cancer Is Modulated by the Base Excision Repair Interaction Network
Critical Reviews™ in Oncogenesis, Vol.14, 2008, issue 4
Katarzyna D. Arczewska, Hilde Nilsen, Katerina Michalickova, Ian M. Donaldson
Tumor Suppressor Roles of the Denitrosylase GSNOR
Critical Reviews™ in Oncogenesis, Vol.21, 2016, issue 5-6
Salvatore Rizza, Giuseppe Filomeni
Multifaceted Modulation of SIRT1 in Cancer and Inflammation
Critical Reviews™ in Oncogenesis, Vol.20, 2015, issue 1-2
Yun Lu, Xi Chen, Guangwei Liu, Hui Yang, Yujing Bi, Zhengguo Zhang, Yiwei Chu, Jian Wang, Ruifu Yang, Ruoning Wang, Lixiang Xue
Long-Term Effects of Chromatin Remodeling and DNA Damage in Stem Cells Induced by Environmental and Dietary Agents
Journal of Environmental Pathology, Toxicology and Oncology, Vol.32, 2013, issue 4
C. Greer Vestal, Christine Richardson, Bhawana Bariar
Expression and Activity of Aryl Hydrocarbon Receptors in Development and Cancer
Critical Reviews™ in Eukaryotic Gene Expression, Vol.18, 2008, issue 4
Loretta L. Collins, Ellen C. Henry, Thomas A. Gasiewicz