TY - JOUR
T1 - DNA repair efficiency in transgenic mice over expressing ribosomal protein S3
AU - Hegde, Vijay
AU - Yadavilli, Sridevi
AU - McLaughlin, Leslie D.
AU - Deutsch, Walter A.
N1 - Funding Information:
This work utilized the facilities of the Cell Biology and Bioimaging Core that are supported in part by COBRE (NIH P20-RR021945) and CNRU (NIH 1P30-DK072476) center grants from the National Institutes of Health. This work was supported in part by a supplement to US Public Health Service grant CA 109798 to WAD and a pilot and feasibility grant from the division of Nutrition and Chronic Diseases, Pennington Biomedical Research center to VH. This research was conducted while Vijay Hegde was an AFAR Research grant recipient. We would like to acknowledge and thank one of the reviewers of our manuscript for suggesting the possibility of RPS3 binding to 8-oxoG:A mispairs and blocking OGG1 until MYH can remove the misincorporated adenine.
PY - 2009/6/18
Y1 - 2009/6/18
N2 - 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.
AB - 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.
KW - Oxidative DNA damage
KW - Ribosomal protein S3
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=67349134259&partnerID=8YFLogxK
U2 - 10.1016/j.mrfmmm.2009.03.005
DO - 10.1016/j.mrfmmm.2009.03.005
M3 - Article
C2 - 19481675
AN - SCOPUS:67349134259
VL - 666
SP - 16
EP - 22
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
SN - 0027-5107
IS - 1-2
ER -