DNA repair efficiency in transgenic mice over expressing ribosomal protein S3.
Human ribosomal protein S3 (RPS3) has previously been shown to have alternative roles beyond its participation in protein synthesis. For example, our in vitro studies have shown that RPS3 has an extraordinarily high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG). Notably, in cells exposed to oxidative stress RPS3 translocates to the nucleus where it co-localizes with foci of 8-oxoG. We have engineered transgenic mice over expressing RPS3 in an attempt to determine the outcome of RPS3 translocation in a whole animal. Mouse embryonic fibroblasts (MEFs) isolated from these transgenic mice showed an increased accumulation of DNA damage in cells exposed to oxidative damage when compared to MEFs from wild-type mice. In MEFs exposed to oxidative stress we observed the translocation of RPS3 from the cytoplasm to the nucleus and co-localizing to 8-oxoG foci, an observation that could involve the blocking of the repair of this mutagenic base and thereby explain why transgenic MEFs exposed to oxidative stress have higher levels of DNA damage.
Hegde
Vijay
V
DNA Damage and Repair Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA. hegdev@pbrc.edu
Yadavilli
Sridevi
S
McLaughlin
Leslie D
LD
Deutsch
Walter A
WA
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D003849:Deoxyguanosine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology; D012269:Ribosomal Proteins / Q000378:metabolism*; D015854:Up-Regulation
D012269:Ribosomal Proteins; C044152:ribosomal protein S3; D003849:Deoxyguanosine