RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response.
The post-translational modification of DNA repair and checkpoint proteins by ubiquitin and small ubiquitin-like modifier (SUMO) critically orchestrates the DNA damage response (DDR). The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin, through its selective recognition and ubiquitination of SUMO-modified proteins. Here, we define a key new determinant for target discrimination by RNF4, in addition to interaction with SUMO. We identify a nucleosome-targeting motif within the RNF4 RING domain that can bind DNA and thereby enables RNF4 to selectively ubiquitinate nucleosomal histones. Furthermore, RNF4 nucleosome-targeting is crucially required for the repair of TRF2-depleted dysfunctional telomeres by 53BP1-mediated non-homologous end joining.
Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA.
Lynda M
LM
Groocock
Minghua
M
Nie
John
J
Prudden
Davide
D
Moiani
Tao
T
Wang
Anton
A
Cheltsov
Robert P
RP
Rambo
Andrew S
AS
Arvai
Chiharu
C
Hitomi
John A
JA
Tainer
Karolin
K
Luger
J Jefferson P
JJ
Perry
Eros
E
Lazzerini-Denchi
Michael N
MN
Boddy
D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D018360:Crystallography, X-Ray; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D055786:Gene Knockout Techniques; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*; D009707:Nucleosomes / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D016615:Telomere / Q000187:drug effects / Q000235:genetics; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*; D000071857:Tumor Suppressor p53-Binding Protein 1; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; D025841:Small Ubiquitin-Related Modifier Proteins; C534796:TRF2 protein, mouse; D035341:Telomeric Repeat Binding Protein 2; D014157:Transcription Factors; C498302:Trp53bp1 protein, mouse; D000071857:Tumor Suppressor p53-Binding Protein 1; D025801:Ubiquitin; D013629:Tamoxifen; C016601:afimoxifene; C486410:Rnf4 protein, mouse; D044767:Ubiquitin-Protein Ligases