53BP1 Antibody - #AF6817

Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis. Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1. In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites. Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites. Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs. Participates to the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1.

Asymmetrically dimethylated on Arg residues by PRMT1. Methylation is required for DNA binding.

Phosphorylated at basal level in the absence of DNA damage. Phosphorylated by ATM in response to DNA damage: phosphorylation at different sites promotes interaction with different set of proteins: phosphorylation at the N-terminus by ATM (residues from 6-178) promotes interaction with PAXIP1 and non-homologous end joining (NHEJ) of dysfunctional telomeres. Phosphorylation by ATM at residues that are located more C-terminus (residues 300-650) leads to promote interaction with RIF1. Interaction with RIF1 leads to disrupt interaction with NUDT16L1/TIRR. Phosphorylation at Thr-1609 and Ser-1618 in the UDR motif blocks interaction with H2AK15ub. Dephosphorylated by PPP4C. Hyperphosphorylation during mitosis correlates with its exclusion from chromatin and DNA lesions. Hyperphosphorylated in an ATR-dependent manner in response to DNA damage induced by UV irradiation. Dephosphorylated by PPP5C.

Nucleus. Chromosome. Chromosome>Centromere>Kinetochore.
Note: Localizes to the nucleus in absence of DNA damage (PubMed:28241136). Following DNA damage, recruited to sites of DNA damage, such as double stand breaks (DSBs): recognizes and binds histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:23333306, PubMed:23760478, PubMed:24703952, PubMed:28241136, PubMed:17190600). Associated with kinetochores during mitosis (By similarity).

Homoligomer. Interacts with p53/TP53 (via the central domain). Interacts with DCLRE1C. Interacts with histone H2AX and this requires phosphorylation of H2AX on 'Ser-139'. Interacts with histone H4 that has been dimethylated at 'Lys-20' (H4K20me2). Has low affinity for histone H4 containing monomethylated 'Lys-20' (H4K20me1). Does not bind histone H4 containing unmethylated or trimethylated 'Lys-20' (H4K20me3). Has low affinity for histone H3 that has been dimethylated on 'Lys-79'. Has very low affinity for histone H3 that has been monomethylated on 'Lys-79' (in vitro). Does not bind unmethylated histone H3. Interacts with histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub). Interacts with PWWP3A/EXPAND1. Interacts with CHEK2; modulates CHEK2 phosphorylation at 'Thr-68' in response to infrared. Interacts with MSL1; this interaction may be required for MSL1 DNA repair activity, but not for histone acetyltransferase activity. Interacts (when phosphorylated by ATM) with RIF1. Interacts (via the Tudor-like domain) with NUDT16L1/TIRR; interaction masks the Tudor-like domain and prevents recruitment to chromatin. Interacts with PAXIP1. Interacts with IFI202A (By similarity). Interacts with SHLD2.

The Tudor-like region mediates binding to histone H4 dimethylated at 'Lys-20' (H4K20me2) (PubMed:17190600). Interaction with NUDT16L1/TIRR masks the Tudor-like domain and prevents recruitment to chromatin (PubMed:28241136).

The UDR (ubiquitin-dependent recruitment) motif specifically recognizes and binds histone H2A monoubiquitinated at 'Lys-15' (H2AK15ub) (PubMed:23760478, PubMed:24703952). Phosphorylation of the UDR blocks interaction with H2AK15ub (PubMed:24703952).