RAD18-BRCTx interaction is required for efficient repair of UV-induced DNA damage.
BRCA1 carboxyl-terminal (BRCT) motifs are present in a number of proteins involved in DNA repair and/or DNA damage signaling pathways. The BRCT domain-containing protein BRCTx has been shown to interact physically with RAD18, an E3 ligase involved in postreplication repair and homologous recombination repair. However, the physiological relevance of the interaction between RAD18 and BRCTx is largely unknown. In this study, we showed that RAD18 interacts with BRCTx in a phosphorylation-dependent manner and that this interaction, mediated via highly conserved serine residues on the RAD18 C terminus, is required for BRCTx accumulation at DNA damage sites. Furthermore, we uncovered critical roles of the RAD18-BRCTx module in UV-induced DNA damage repair but not PCNA mono-ubiquitination or homologous recombination. Thus, our results suggest that RAD18 has an additional function in the surveillance of the UV-induced DNA damage response signal.
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.
Ting
T
Liu
Hongxia
H
Chen
Hongtai
H
Kim
Michael S Y
MS
Huen
Junjie
J
Chen
Jun
J
Huang
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010766:Phosphorylation / Q000528:radiation effects; D011485:Protein Binding / Q000528:radiation effects; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000528:radiation effects; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases; D014466:Ultraviolet Rays
C572169:BRCTx protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C485954:RAD18 protein, human; D044767:Ubiquitin-Protein Ligases