5ECG

Crystal structure of the BRCT domains of 53BP1 in complex with p53 and H2AX-pSer139 (gammaH2AX)

Summary for 5ECG

• Entry DOI: 10.2210/pdb5ecg/pdb
• Descriptor: Cellular tumor antigen p53, Tumor suppressor p53-binding protein 1, SEP-GLN-GLU-TYR, ... (5 entities in total)
• Functional Keywords: dna repair, nhej, h2ax, brct, antitumor protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637; Nucleus: Q12888
• Total number of polymer chains: 6
• Total formula weight: 110952.06

Authors

Day, M.,Oliver, A.W.,Pearl, L.H. (deposition date: 2015-10-20, release date: 2015-12-16, Last modification date: 2024-01-10)

Primary citation

Baldock, R.A.,Day, M.,Wilkinson, O.J.,Cloney, R.,Jeggo, P.A.,Oliver, A.W.,Watts, F.Z.,Pearl, L.H.
ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with gamma H2AX.
Cell Rep, 13:2081-2089, 2015

PubMed Abstract: 53BP1 plays multiple roles in mammalian DNA damage repair, mediating pathway choice and facilitating DNA double-strand break repair in heterochromatin. Although it possesses a C-terminal BRCT2 domain, commonly involved in phospho-peptide binding in other proteins, initial recruitment of 53BP1 to sites of DNA damage depends on interaction with histone post-translational modifications--H4K20me2 and H2AK13/K15ub--downstream of the early γH2AX phosphorylation mark of DNA damage. We now show that, contrary to current models, the 53BP1-BRCT2 domain binds γH2AX directly, providing a third post-translational mark regulating 53BP1 function. We find that the interaction of 53BP1 with γH2AX is required for sustaining the 53BP1-dependent focal concentration of activated ATM that facilitates repair of DNA double-strand breaks in heterochromatin in G1.

PubMed: 26628370
DOI: 10.1016/j.celrep.2015.10.074

Experimental method

X-RAY DIFFRACTION (3 Å)