Abstract
The integrity of the genome is essential to the health of the individual and to the reproductive success of a species. Transmission of genetic information is in a selective balance between two opposing forces, the maintenance of genetic stability versus elimination of mutational change and loss of evolutionary potential. Caenorhabditis elegans provides many advantages for the study of DNA surveillance and repair in a multicellular organism. Several genes have been identified by mutagenesis and RNA interference that affect DNA damage checkpoint and repair functions. Many of these DNA damage response genes also play essential roles in DNA replication, cell cycle control, development, meiosis and mitosis. To date, no obvious DNA damage-induced checkpoint has been described in C. elegans somatic cells. In contrast, the DNA damage response in the germ line is characterized by two spatially separate checkpoints; mitotic germ nuclei proliferation arrest and apoptosis of damaged meiotic nuclei. Both of these responses are regulated by checkpoint genes including mrt-2, hus-1, rad-5 and cep-1, the C. elegans ortholog of the human tumour suppressor p53. The germ line DNA damage checkpoints in C. elegans provide an excellent model in which to study the genes required to maintain genomic stability and to test compounds which might have tumor suppressing properties. In addition to single gene studies, integration of data from high-throughput screens has identified genes not previous implicated in the DNA damage response and elucidated novel connections between the different repair pathways. Most of the genes involved are conserved between worms and humans, and in humans, are associated with either oncogenesis or tumor-suppression. Thus, studies of the physical and functional interactions of the components of the repair pathways in C. elegans will provide information about human repair disorders and cancer predisposition.
Highlights
Gene rad-1 rad-2 rad-3 rad-4 rad-6 rad-7 rad-8 rad-9 xpa-1 XPB XPC XPD XPE XPF XPG ERCC1 csb-1
Radiation sensitivity of C. elegans In C. elegans, the first study of repair function was the identification by Hartman and Herman (1982) of nine Rad mutants, which were hypersensitive to ultraviolet light during embryogenesis
Researchers have used reverse genetic techniques such as RNA interference and PCR-mediated gene knockouts to investigate genes involved in different DNA damage response pathways such as nucleotide excision repair (Park et al, 2002; Park et al, 2004; Lee et al, 2002)
Summary
The integrity of the genome is essential to the health of the individual and to the reproductive success of a species. Caenorhabditis elegans provides an experimental model in which the repair processes required for both genomic stability and mutational change can be studied. In this Chapter, we present an overview of DNA damage response research using Caenorhabditis elegans. UV irradiation of the Rad mutants results in a decrease in viability Many of these Rad mutants exhibit phenotypes in addition to their UV sensitivity suggesting that the Rad genes are involved in other biological processes in addition to their roles in the UV-induced DNA damage response (Table 1). The UV hypersensitivity of the early stage embryo might be due in part to the rapid cell proliferation and the lack of obvious DNA damage-induced checkpoints; DNA replication progresses even after exposure to large fluences of UV radiation (Jones and Hartman, 1996)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
