| RRC ID |
82837
|
| Author |
Katsuki Y, Abe M, Park SY, Wu W, Yabe H, Yabe M, van Attikum H, Nakada S, Ohta T, Seidman MM, Kim Y, Takata M.
|
| Title |
RNF168 E3 ligase participates in ubiquitin signaling and recruitment of SLX4 during DNA crosslink repair.
|
| Journal |
Cell Rep
|
| Abstract |
SLX4/FANCP is a key Fanconi anemia (FA) protein and a DNA repair scaffold for incision around a DNA interstrand 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.
|
| Volume |
37(4)
|
| Pages |
109879
|
| Published |
2021-10-26
|
| DOI |
10.1016/j.celrep.2021.109879
|
| PII |
S2211-1247(21)01349-8
|
| PMID |
34706224
|
| PMC |
PMC11388903
|
| MeSH |
DNA Repair*
Digoxigenin / pharmacology
Ficusin / pharmacology
HCT116 Cells
Humans
MCF-7 Cells
Mitomycin / pharmacology
Recombinases / genetics
Recombinases / metabolism*
Signal Transduction*
Ubiquitin / genetics
Ubiquitin / metabolism*
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism*
|
| IF |
8.109
|
| Resource |
| DNA material |
CSII-CMV-MCS-IRES2-Bsd (RDB04385) |
