ZRF1 mediates remodeling of E3 ligases at DNA lesion sites during nucleotide excision repair.
Faithful DNA repair is essential to maintain genome integrity. Ultraviolet (UV) irradiation elicits both the recruitment of DNA repair factors and the deposition of histone marks such as monoubiquitylation of histone H2A at lesion sites. Here, we report how a ubiquitin E3 ligase complex specific to DNA repair is remodeled at lesion sites in the global genome nucleotide excision repair (GG-NER) pathway. Monoubiquitylation of histone H2A (H2A-ubiquitin) is catalyzed predominantly by a novel E3 ligase complex consisting of DDB2, DDB1, CUL4B, and RING1B (UV-RING1B complex) that acts early during lesion recognition. The H2A-ubiquitin binding protein ZRF1 mediates remodeling of this E3 ligase complex directly at the DNA lesion site, causing the assembly of the UV-DDB-CUL4A E3 ligase complex (DDB1-DDB2-CUL4A-RBX1). ZRF1 is an essential factor in GG-NER, and its function at damaged chromatin sites is linked to damage recognition factor XPC. Overall, the results shed light on the interplay between epigenetic and DNA repair recognition factors at DNA lesion sites.
Laboratory of Molecular Epigenetics, Institute of Molecular Biology, 55128 Mainz, Germany.
Ekaterina
E
Gracheva
Laboratory of Molecular Epigenetics, Institute of Molecular Biology, 55128 Mainz, Germany.
Shalaka
S
Chitale
Laboratory of Molecular Epigenetics, Institute of Molecular Biology, 55128 Mainz, Germany.
Thomas
T
Wilhelm
Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany.
Alexander
A
Rapp
Laboratory of Molecular Epigenetics, Institute of Molecular Biology, 55128 Mainz, Germany.
Jonathan
J
Byrne
Laboratory of Molecular Epigenetics, Institute of Molecular Biology, 55128 Mainz, Germany.
Jens
J
Stadler
Laboratory of Molecular Epigenetics, Institute of Molecular Biology, 55128 Mainz, Germany.
Rebeca
R
Medina
Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany.
M Cristina
MC
Cardoso
Laboratory of Molecular Epigenetics, Institute of Molecular Biology, 55128 Mainz, Germany h.richly@imb-mainz.de.
Holger
H
Richly
D044842:Cullin Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism / Q000502:physiology; D016601:RNA-Binding Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D014466:Ultraviolet Rays
C517832:CUL4B protein, human; D044842:Cullin Proteins; C091435:DDB1 protein, human; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; C414672:DNAJC2 protein, human; D006657:Histones; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D016601:RNA-Binding Proteins; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human; D044767:Ubiquitin-Protein Ligases