상세 보기
- Katsuki, Yoko;
- Abe, Masako;
- Park, Seon Young;
- Wu, Wenwen;
- Yabe, Hiromasa;
- ... Kim, Yonghwan;
- 외 6명
WEB OF SCIENCE
10SCOPUS
10초록
SLX4/FANCP is a key Fanconi anemia (FA) protein and a DNA repair scaffold for incision around a DNA inter strand crosslink (ICL) by its partner XPF nuclease. The tandem UBZ4 ubiquitin-binding domains of SLX4 are critical for the recruitment of SLX4 to damage sites, likely by binding to K63-linked polyubiquitin chains. However, the identity of the ubiquitin E3 ligase that mediates SLX4 recruitment remains unknown. Using small interfering RNA (siRNA) screening with a GFP-tagged N-terminal half of SLX4 (termed SLX4-N), we identify the RNF168 E3 ligase as a critical factor for mitomycin C (MMC)-induced SLX4 foci formation. RNF168 and GFP-SLX4-N colocalize in MMC-induced ubiquitin foci. Accumulation of SLX4-N at psoralen-laser ICL tracks or of endogenous SLX4 at Digoxigenin-psoralen/UVA ICL is dependent on RNF168. Finally, we find that RNF168 is epistatic with SLX4 in promoting MMC tolerance. We conclude that RNF168 is a critical component of the signal transduction that recruits SLX4 to ICL damage.
키워드
- 제목
- RNF168 E3 ligase participates in ubiquitin signaling and recruitment of SLX4 during DNA crosslink repair
- 저자
- Katsuki, Yoko; Abe, Masako; Park, Seon Young; Wu, Wenwen; Yabe, Hiromasa; Yabe, Miharu; van Attikum, Haico; Nakada, Shinichiro; Ohta, Tomohiko; Seidman, Michael M.; Kim, Yonghwan; Takata, Minoru
- 발행일
- 2021-10-26
- 유형
- Article
- 저널명
- Cell Reports
- 권
- 37
- 호
- 4
- 페이지
- 1 ~ 21