DNA Damage Pathways

Overview of DNA damage repair mechanisms

DNA is constantly exposed to a variety of damaging factors such as genotoxic agents, environmental factors (e.g. UV light, irradiation) or normal metabolic activities (e.g. nucleotide mis-incorporation during DNA replication, reactive oxygen species) that causes a range of lesions. DNA repair pathways are constantly active in the cell to identify and correct all DNA damage that may occur. The wide diversity of DNA lesions requires multiple, largely distinct DNA repair processes.

The DNA repair machinery is vital for the maintenance of genome integrity and for the proper function and survival of all organisms. A cell that has accumulated a large number of lesions can either undergo apoptosis, senescence, or in the case of cancers; unregulated cell division. A failure to repair DNA lesions can result in mutagenesis, large scale genome aberrations and cellular cytotoxicity.

This collection has been generated in close collaboration with Joanna I. Loizou (CeMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria).

Case study

The response of LIG4 (LIGIV) and PRKDC (DNA-PKc) (-/-) cell lines to treatment with Etoposide was studied. These proteins play a role in Non-Homologous End Joining (NHEJ) and they are both associated with disease; LIG4 is associated with T cell leukemia whilst loss of PRKDC has been linked to gastric tumors.

LIG4 and PRKDC (-/-) cells show selective sensitivity to Etoposide over HCT116 Parental cells in an 8 day colony forming assay and a 96 hour proliferation assay.

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Cell lines used

Examples of popular knockout cell lines for DNA damage