6RML

Crystal structure of TOPBP1 BRCT0,1,2 in complex with a 53BP1 phosphopeptide

6RML の概要

• エントリーDOI: 10.2210/pdb6rml/pdb
• 分子名称: DNA topoisomerase 2-binding protein 1, 53BP1 (2 entities in total)
• 機能のキーワード: brct domain phosphopeptide recognition, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69538.52

構造登録者

Day, M.,Oliver, A.W.,Pearl, L.H. (登録日: 2019-05-07, 公開日: 2019-06-12, 最終更新日: 2024-11-13)

主引用文献

Bigot, N.,Day, M.,Baldock, R.A.,Watts, F.Z.,Oliver, A.W.,Pearl, L.H.
Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.
Elife, 8:-, 2019

PubMed Abstract: Coordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ubiquitylation on other proteins, and are themselves carriers of such regulatory signals. Here we show that the DNA damage checkpoint regulating S-phase entry is controlled by a phosphorylation-dependent interaction of 53BP1 and TOPBP1. BRCT domains of TOPBP1 selectively bind conserved phosphorylation sites in the N-terminus of 53BP1. Mutation of these sites does not affect formation of 53BP1 or ATM foci following DNA damage, but abolishes recruitment of TOPBP1, ATR and CHK1 to 53BP1 damage foci, abrogating cell cycle arrest and permitting progression into S-phase. TOPBP1 interaction with 53BP1 is structurally complimentary to its interaction with RAD9-RAD1-HUS1, allowing these damage recognition factors to bind simultaneously to the same TOPBP1 molecule and cooperate in ATR activation in the G1 DNA damage checkpoint.

PubMed: 31135337
DOI: 10.7554/eLife.44353

実験手法

X-RAY DIFFRACTION (2.81 Å)