repository
Coupled Functions of CTCF in Transcription & Repair in Response to DNA Double-Strand Breaks
- Author(s)
- 윤다미
- Advisor
- 이종수
- Department
- 일반대학원 생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2023-08
- Language
- kor
- Keyword
- CTCF; DNA Double-Strand Breaks; DNA damage repair; NELF-E
- Alternative Abstract
- A variety of factors are commonly or differentially involved in the repair of DNA damage depending on types of DNA insults. Among them, DNA double-strand breaks (DSBs) are the most severe lesions that, if left unrepaired, can lead to serious genome aberrations, potentially affecting cell survival. Two major DSB repair pathways include non-homologous end joining (NHEJ) and homologous recombination (HR). At the vicinity of DSBs occurring within transcriptional active regions of the genome, several HR proteins are preferentially recruited and DNA-RNA hybrid R loop structures are formed via the negative elongation factor NELF-dependent transient transcription suppression. Little is known about the mechanisms that ensure coupled transcription suppression and HR-mediated repair in response to DSBs. <br> In this study, I identified the multifunctional transcriptional factor CCCTC-binding factor (CTCF), which engages in the initial step in HR by recruiting the resection endonuclease CtIP, as a crucial factor that facilitates the rapid recruitment of NELF-E and its resultant R-loop formation via transcription suppression at DSBs. CTCF interacts with NELF-E. Depletion of CTCF attenuates DSB recruitment of NELF-E and resultantly impairs the DSB-induced transcriptional suppression and R-loop generation at DSBs. Either CTCF or NELF-E depletion impairs recruitment of several HR factors including BARD1, BRCA1, and RAD51, and heterochromatin protein1γ (HP1γ) at DSBs, thereby resulting in compromised DSB R-loop formation and HR. However, NELF-E depletion has little effects on the CTCF recruitment at DSB, suggesting that CTCF acts upstream of NELF-E and R-loop in the HR pathway. <br> Overall, my findings demonstrate that CTCF directs rapid and transient transcription suppression and HR-mediated repair of DSBs at transcriptionally active regions through establishing CTCF-NELF-HR factor axis.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Bioscience > 3. Theses(Master)
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
-
- License
- STATISTICS
- Total Visit :4,972,906
- Total Download :2,093
- Today View :5,579
