Role of DNA repair in the protection against genotoxic stress

Abstract

Abstract. The genome of all organisms is constantly attacked by a variety of environmental and endogenous mutagens that cause cell death, apoptosis, senescence, genetic diseases and cancer. To mitigate these deleterious endpoints of genotoxic reactions, living organisms have evolved one or more mechanisms for repairing every type of naturally occurring DNA lesion. For example, double-strand breaks are rapidly religated by non-homologous end-joining. Homologous recombination is used for the high-fidelity repair of interstrand cross-links, double-strand breaks and other DNA injuries that disrupt the replication fork. Some genotoxic lesions inflicted by alkylating agents can be repaired by direct reversal of DNA damage. The base excision repair pathway takes advantage of multiple DNA glycosylases to remove modified or incorrect bases. Finally, the nucleotide excision repair machinery provides a versatile strategy to monitor DNA quality and eliminate all forms of helix-distorting DNA lesions, including a wide diversity of carcinogen adducts. The efficiency of DNA repair responses is enhanced by their coupling to transcription and coordination with the cell cycle circuit.

Mechanisms in cadmium-induced carcinogenicity: recent insights

“…DNA glycosylases act specifically on one or few substrates, and BER is mainly responsible for the removal of different types of endogenous DNA damage, including oxidative DNA base modifications. This process generates abasic (AP) sites, which are further processed in a multistep process with slight differences depending on the type of damage (de Boer and Hoeijmakers 2000; Christmann et al 2003;Hakem 2008;Camenisch and Naegeli 2009). One other DNA repair system essential for maintaining genomic stability is the DNA mismatch repair system (MMR).…”

“…While DNA excision repair systems are predominantly error-free, DNA damage persisting at the time of DNA replication may also be converted into mutations due to error-prone bypass mechanisms. Also, DNA double strand break repair may be highly error prone, especially NHEJ (de Boer and Hoeijmakers 2000; Christmann et al 2003;Camenisch and Naegeli 2009;Kerzendorfer and O'Driscoll 2009).…”

Molecular mechanisms underlying chemical liver injury

“…Lipid peroxides are repaired by a complex process that operates in concert with a series of reductants along with GSH peroxidase and GSH reductase. Different types of damage to DNA are corrected by specialised mechanisms, each using a different set of repair proteins (Refs 99, 100, 101). Despite its high reactivity with electrophiles and free radicals, nuclear DNA is remarkably stable, in part because it is packaged in chromatin and because of the several repair mechanisms that correct alterations in DNA.…”

Mechanisms of Cadmium Carcinogenicity in the Gastrointestinal Tract

“…This process generates a basic (AP) site, which is further processed in a multistep process with slight differences depending on the type of damage (de Boer and Hoeijmakers, 2000;Christmann et al, 2003;Hakem, 2008;Camenisch and Naegeli, 2009). BER mainly corrects non-bulky lesions produced by alkylation, oxidation or deamination (Memisoglu and Samson, 2000;Nilsen and Krokan, 2001).…”