TY - JOUR
T1 - Translocation of human ribosomal protein S3 to sites of DNA damage is dependant on ERK-mediated phosphorylation following genotoxic stress
AU - Yadavilli, Sridevi
AU - Hegde, Vijay
AU - Deutsch, Walter A.
N1 - Funding Information:
We especially want to thank Dr. Stuart Linn for his continued interest in the multifunctional roles of hS3. We thank Dr. Weihong Pan, Blood Brain Barrier laboratory, PBRC for use of the microscopy facility. This research was supported by US Public Health Service Grant CA 109798 to WAD.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - Besides its role in translation and ribosome maturation, human ribosomal protein S3 (hS3) is implicated in DNA damage recognition as reflected by its affinity for abasic sites and 7,8-dihydro-8-oxoguanine (8-oxoG) residues in DNA in vitro. Here, we demonstrate that hS3 is capable of carrying out both roles by its ex vivo translocation from the cytoplasm to the nucleus as a consequence of genotoxic stress. The translocation of hS3 is dependent on ERK1/2-mediated phosphorylation of a threonine residue (T42) of hS3. Two different ectopically expressed site-directed mutants of T42 failed to respond to conditions of genotoxic stress, thus providing a link between DNA damage and ERK1/2 dependent phosphorylation of hS3. Lastly, hS3 was traced in exposed cells to its co-localization with 8-oxoG foci, raising the possibility that hS3 is a member of a cellular DNA damage response pathway that results in its interaction with sites of DNA damage.
AB - Besides its role in translation and ribosome maturation, human ribosomal protein S3 (hS3) is implicated in DNA damage recognition as reflected by its affinity for abasic sites and 7,8-dihydro-8-oxoguanine (8-oxoG) residues in DNA in vitro. Here, we demonstrate that hS3 is capable of carrying out both roles by its ex vivo translocation from the cytoplasm to the nucleus as a consequence of genotoxic stress. The translocation of hS3 is dependent on ERK1/2-mediated phosphorylation of a threonine residue (T42) of hS3. Two different ectopically expressed site-directed mutants of T42 failed to respond to conditions of genotoxic stress, thus providing a link between DNA damage and ERK1/2 dependent phosphorylation of hS3. Lastly, hS3 was traced in exposed cells to its co-localization with 8-oxoG foci, raising the possibility that hS3 is a member of a cellular DNA damage response pathway that results in its interaction with sites of DNA damage.
KW - Base excision repair
KW - ERK
KW - Genotoxic stress
KW - Nuclear translocation
KW - Ribosomal protein S3
UR - http://www.scopus.com/inward/record.url?scp=34548541557&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2007.04.009
DO - 10.1016/j.dnarep.2007.04.009
M3 - Article
C2 - 17560175
AN - SCOPUS:34548541557
SN - 1568-7864
VL - 6
SP - 1453
EP - 1462
JO - DNA Repair
JF - DNA Repair
IS - 10
ER -