DNA endonuclease RBBP8
Also known as: CTIP, RBBP8
Function
Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). Specifically promotes the endonuclease activity of the MRN complex to clear DNA ends containing protein adducts: recruited to DSBs by NBN following phosphorylation by CDK1, and promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends. Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage. During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity). Binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging.
Classification
- Family (Pfam)
- PF10482 CtIP_N, PF08573 SAE2
- InterPro
- CtIP_N, Ctp1_C, RBBP8-like
- Functional cluster
- Zinc-Finger & Chromatin Regulatory Proteins
Experimental structures · PDB · 4
A predicted model is available from AlphaFold.
Gene Ontology · 17
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0035861 site of double-strand break
- GO:0017053 transcription repressor complex
- GO:0003684 damaged DNA binding
- GO:0042802 identical protein binding
- GO:0046872 metal ion binding
- GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
- GO:0000014 single-stranded DNA endodeoxyribonuclease activity
- GO:0003714 transcription corepressor activity
- GO:0051301 cell division
- GO:0010792 DNA double-strand break processing involved in repair via single-strand annealing
- GO:0110025 DNA strand resection involved in replication fork processing
- GO:0000724 double-strand break repair via homologous recombination
- GO:0035825 homologous recombination
- GO:0051321 meiotic cell cycle
- GO:0044818 mitotic G2/M transition checkpoint
Disease associations
- Jawad syndrome MONDO:0009622
- Seckel syndrome 2 MONDO:0011715
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- DNA endonuclease RBBP8 0.98
- DNA endonuclease RBBP8 0.98
- DNA endonuclease RBBP8 0.96
- DNA endonuclease RBBP8 0.94
- DNA endonuclease RBBP8 0.94
- Mis18-binding protein 1 0.88
- DNA endonuclease RBBP8 0.86
- DNA polymerase zeta catalytic subunit 0.85
- Breast cancer type 1 susceptibility protein homolog 0.84
- Breast cancer type 1 susceptibility protein homolog 0.84
- DNA damage-induced apoptosis suppressor protein 0.84
- Breast cancer type 1 susceptibility protein homolog 0.83
Co-cited proteins · studied together in the literature
- DNA endonuclease RBBP8 2 shared papers
- DNA endonuclease RBBP8 3 shared papers
- Aurora kinase A- and ninein-interacting protein 1 shared papers
- E3 ubiquitin-protein ligase RNF138 1 shared papers
- Lymphoid-specific helicase 1 shared papers
- Nibrin 5 shared papers
- Breast cancer type 1 susceptibility protein 4 shared papers
- Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 2 shared papers
- Poly-ADP-ribosylation-amplifying and CtIP-maintaining micropeptide 1 shared papers
- Double-strand break repair protein MRE11 5 shared papers
- Kelch-like protein 15 2 shared papers
- DNA endonuclease ctp1 1 shared papers
Literature · 51 cited papers
- Micropeptide PACMP inhibition elicits synthetic lethal effects by decreasing CtIP and poly(ADP-ribosyl)ation. Mol. Cell · 2022
- Structural basis for the coiled-coil architecture of human CtIP. Open Biol. · 2021
- A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity. Proc. Natl. Acad. Sci. U.S.A. · 2021
- The human HELLS chromatin remodelling protein promotes end resection to facilitate homologous recombination and contributes to DSB repair within heterochromatin. Nucleic Acids Res. · 2020
- PMID 30975768 Science · 2019
- NBS1 promotes the endonuclease activity of the MRE11-RAD50 complex by sensing CtIP phosphorylation. EMBO J. · 2019
- CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair. Elife · 2019
- AUNIP/C1orf135 directs DNA double-strand breaks towards the homologous recombination repair pathway. Nat. Commun. · 2017
- SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous recombination. Cell Rep. · 2017
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- Phosphorylated CtIP functions as a co-factor of the MRE11-RAD50-NBS1 endonuclease in DNA end resection. Mol. Cell · 2016
- Nbs1 converts the human Mre11/Rad50 nuclease complex into an endo/exonuclease machine specific for protein-DNA adducts. Mol. Cell · 2016
- … and 39 more in the literature graph