Henok Kassahun et al. (2008) European Worm Meeting "Role of Base Excision Repair in the DNA damage response"

Tanima Sengupta, Marlene Dengg, Hilde Nilsen, Henok Kassahun

[European Worm Meeting, 2008]

The C. elegans germ line has been used extensively to dissect the. signalling pathways that regulate DNA damage responses. Germ cell apoptosis. and transient mitotic cell-cycle arrest are trigged in response to. genotoxic stresses. In contrast little is known about DNA repair. Base. excision repair (BER) is the major pathway for repair oxidative DNA damage.. Here, damaged bases are recognized by DNA glycosylases. Human cells encode. 12 DNA glycosylases. In C. elegans, there is a striking under-. representation of DNA glycosylases as only the NTH-1 and UNG-1 enzymes seem. to be present. We have isolated an ung-1 (qa7600) mutant and here, we will. show the phenotypic characterization of this mutant and the nth-1 (ok724). mutant. We have tested whether BER contributes to survival in response to. oxidative stress and whether it impacts on life span. Moreover, we have. investigated the role of BER in apoptotic signalling and provide evidence. that BER enzymes participate in DNA damage response by promoting apoptosis.

Dengg M. et al. (2006) European Worm Meeting "Using Caenorhabditis elegans to Study Cellular Responses to Endogenous DNA Damage"

Boulton S., Nilsen H., Garcia-Muse T., Dengg M.

[European Worm Meeting, 2006]

Dengg, M. 1, Garcia-Muse, T.2, Boulton, S.2, and Nilsen, H1 DNA repair pathways and intracellular signalling cascades contribute to DNA damage response (DDR) mechanisms that determine cellular responses to DNA damage. C.elegans has been used successfully to study DDR in response to DNA damage induced by physical or chemical agents. Whether DDR is activated in response to the most abundant forms of DNA damage, arising spontaneously through the reaction of water and reactive oxygen species with DNA, is poorly understood. Compared with treatment with physical or chemical DNA damaging agents, the study of DDR in response to endogenous lesions must overcome technical problems with respect to inducing sufficiently high levels of DNA lesions to allow studies of downstream responses. We have exploited RNA interference (RNAi) technology in C.elegans to modulate dUTP pools in order to achieve incorporation of uracil above background levels. Here, we present data describing the phenotypical consequences of increased incorporation of uracil into DNA. The role of DNA repair and DNA damage checkpoints in activating DNA damage response pathways in response to uracil will be presented.