The Role of YB-1 in DNA Repairing System

• Main Authors: Chen-Che Chiu, 邱辰哲
• Other Authors: Yan-Hwa Wu Lee
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/56199172334328830013

碩士 === 國立陽明大學 === 生物化學研究所 === 92 === Abstract Y-box binding protein-1 (YB-1) is a multi-functional protein involved in several cellular processes including transcription, translation, alternative splicing, virus replication and drug resistance. Since, YB-1 was also found to interact with cisplatin modified-DNA, 8-oxoguanosine and associate with several components of DNA repair system, such as PCNA、DNA polymerse delta and human endonuclease III (hNTH1), YB-1 might involve in DNA repair. However, the precise role of YB-1 in DNA repair is still not fully understood. Here we established YB-1 producing cell line and YB-1 knock-down cell line to determine the role of YB-1 in DNA repair. Using in vivo comet assay, our data indicated that the activity of BER was more activated in YB-1 silencing cells. Consistant with in vivo observation, the in vitro G:U mismatch repair assay also showed the activity of BER was more activated in YB-1 silencing cells. Additionally, the co-localization of PCNA with DNA polymerase delta and YB-1 upon H2O2 treatment was disrupted in YB-1 overexpressing cells treated with H2O2. Moreover, the nuclear localization of hMSH2 upon cisplatin treatment was abrogated in YB-1 overexpressing cells. These results indicate that excess amount of YB-1 may inhibit DNA repair through interfering the proper localization of DNA repair proteins. Together, our finding indicated that YB-1 is a negative regulator of DNA repair system. Deregulated expression of YB-1 in tumor cells may interfere with the behavior of repair machinery, leading to the drug resistance, accumulation of DNA lesions, enhancement of genome instability, and finally cause further progression of tumor cells.