Title Page
Contents
ABSTRACT 9
Ⅰ. Introduction 11
Ⅱ. MATERIALS AND METHODS 14
1. Cell culture and transfection 14
2. Constructs, reagents and antibodies 15
3. MTT assay 16
4. Colony forming assay 16
5. Cell cycle analysis 17
6. Western blot 17
7. Quantitative reverse-transcription PCR 18
8. Immunoprecipitation 19
9. Senescence-associated β-galactosidase assay 20
10. Immunofluorescence and confocal microscopy 20
11. HR and NHEJ assay 21
12. DNA double-strand break reporter assay 21
13. Combination index (CI) and data processing 22
Ⅲ. RESULTS 23
1. PRMT7 inhibition causes growth inhibition in various cancer cells. 23
2. PRMT7 inhibition induces cell cycle arrest and cellular senescence via p21 accumulation. 26
3. PRMT7 regulates DDR. 31
4. PRMT7 regulates DNA repair process. 39
5. PRMT7 inhibitor SGC8158 with doxorubicin potentiates the cytotoxicity. 44
Ⅳ. DISCUSSION 51
Ⅴ. REFERENCE 54
ABSTRACT IN KOREAN 61
Figure 1. PRMT7 inhibition causes growth inhibition in various human cancer cells. 25
Figure 2. PRMT7 inhibition induces cell cycle arrest and cellular senescence via p21 accumulation. 30
Figure 3. PRMT7 regulates DNA damage response. 38
Figure 4. PRMT7 regulates DNA Repair process. 43
Figure 5. SGC8158 potentiates doxorubicin-induced DNA damage response and its cytotoxicity. 50