The PXDLS motif binds to a cleft in CtBP proteins.
The damage-recruitment motif is required for DNA binding and translocation to sites of DNA damage.
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 (PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462, PubMed:23273981, PubMed:26721387, PubMed:27814491, PubMed:27889449, PubMed:30787182). HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse (PubMed:17965729, PubMed:19202191, PubMed:23273981, PubMed:27814491, PubMed:27889449, PubMed:30787182). Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ) (PubMed:19202191). 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 (PubMed:27814491, PubMed:27889449, PubMed:30787182, PubMed:33836577). 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 (PubMed:16581787, PubMed:17965729, PubMed:19759395, PubMed:20064462). Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (PubMed:15485915, PubMed:16818604). 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 (PubMed:30601117).
Seckel syndrome 2
SCKL2
A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability.
None
The disease is caused by variants affecting the gene represented in this entry.
Jawad syndrome
JWDS
A syndrome characterized by congenital microcephaly, moderately severe intellectual disability, and symmetrical digital anomalies. Digital malformations of variable degree include hallux valgus, syndactyly of toes 4 and 5, short fifth fingers, single flexion crease of fifth fingers, polydactyly and synpolydactyly.
None
The disease is caused by variants affecting the gene represented in this entry.
Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk (PubMed:21799032). Associated with sensitivity to tamoxifen in certain breast cancer cell lines (PubMed:18171986).
Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1 (PubMed:10910365, PubMed:17965729). Phosphorylation at Thr-847 by CDK1 is essential for the recruitment to DNA and the DNA repair function (PubMed:19202191, PubMed:27814491, PubMed:27889449). Phosphorylation at Thr-847 and Thr-859 promote interaction with NBN and recruitment to double-strand breaks (DSBs) (PubMed:23273981, PubMed:27814491, PubMed:27889449, PubMed:33836577). Phosphorylated on Ser-327 as cells enter G2 phase (PubMed:15485915). This phosphorylation is required for binding BRCA1 and for the G2/M DNA damage transition checkpoint control (PubMed:15485915). Phosphorylation at Thr-315, probably catalyzed by CDK2, is required for PIN1-binding, while phosphorylation at Ser-276 serves as a PIN1 isomerization site (PubMed:23623683). Phosphorylation at Thr-315 is cell-cycle dependent (PubMed:23623683). It steadily increases during S phase, peaks at late S/G2 phase, and drops at G1 (PubMed:23623683). Phosphorylation is not required for tetramerization (PubMed:30601117). Binds to DNA more strongly when dephosphorylated (PubMed:30601117).
Ubiquitinated (PubMed:14654780, PubMed:16818604, PubMed:27561354). Ubiquitination at multiple sites by BRCA1 (via its N-terminal RING domain) does not lead to its proteasomal degradation but instead the ubiquitinated RBBP8 binds to chromatin following DNA damage and may play a role in G2/M checkpoint control (PubMed:16818604). Ubiquitinated by RNF138 at its N-terminus (PubMed:26502057). Ubiquitinated through 'Lys-48' by the E3 CUL3-KLHL15 complex; this modification leads to proteasomal degradation (PubMed:27561354, PubMed:35219381). Ubiquitinated by the E3 FZR1/APC/C complex; this modification leads to proteasomal degradation (PubMed:25349192).
Belongs to the COM1/SAE2/CtIP family.
Expressed in ER-positive breast cancer lines, but tends to be down-regulated ER-negative cells (at protein level).
CTIP, RBBP8, DNA endonuclease RBBP8, CtBP-interacting protein, Retinoblastoma-binding protein 8, Retinoblastoma-interacting protein and myosin-like, Sporulation in the absence of SPO11 protein 2 homolog, CtIP, RBBP-8, RIM, SAE2
Proteins
Oncology
101942Da
We found 1 product in 1 category