3L40

Crystal Structure of S. pombe Brc1 BRCT5-BRCT6 domains

3L40 の概要

• エントリーDOI: 10.2210/pdb3l40/pdb
• 関連するPDBエントリー: 1jnx 1t2v 2azm 2r1z 3hue 3L41
• 分子名称: BRCT-containing protein 1 (2 entities in total)
• 機能のキーワード: brc1, brct domain, tandem brct repeat, phosphoserine binding domain, dna repair, cell division, mitosis, cell cycle
• 由来する生物種: Schizosaccharomyces pombe (Fission yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49650.79

構造登録者

Williams, R.S.,Williams, J.S.,Guenther, G.,Tainer, J.A. (登録日: 2009-12-18, 公開日: 2010-02-09, 最終更新日: 2024-02-21)

主引用文献

Williams, J.S.,Williams, R.S.,Dovey, C.L.,Guenther, G.,Tainer, J.A.,Russell, P.
gammaH2A binds Brc1 to maintain genome integrity during S-phase.
Embo J., 29:1136-1148, 2010

PubMed Abstract: ATM(Tel1) and ATR(Rad3) checkpoint kinases phosphorylate the C-terminus of histone H2AX (H2A in yeasts) in chromatin flanking DNA damage, establishing a recruitment platform for checkpoint and repair proteins. Phospho-H2A/X (gammaH2A/X)-binding proteins at double-strand breaks (DSBs) have been characterized, but those required for replication stress responses are unknown. Here, we present genetic, biochemical, small angle X-ray scattering (SAXS), and X-ray structural studies of the Schizosaccharomyces pombe Brc1, a 6-BRCT-domain protein that is structurally related to Saccharomyces cerevisiae Rtt107 and mammalian PTIP. Brc1 binds gammaH2A to form spontaneous and DNA damage-induced nuclear foci. Spontaneous Brc1 foci colocalize with ribosomal DNA repeats, a region prone to fork pausing and genomic instability, whereas DNA damage-induced Brc1 foci colocalize with DSB response factors. gammaH2A binding is critical for Brc1 function. The 1.45 A resolution crystal structure of Brc1-gammaH2A complex shows how variable BRCT insertion loops sculpt tandem-BRCT phosphoprotein-binding pockets to facilitate unique phosphoprotein-interaction specificities, and unveils an acidic DNA-mimicking Brc1 surface. From these results, Brc1 docking to gammaH2A emerges as a critical chromatin-specific response to replication-associated DNA damage.

PubMed: 20094029
DOI: 10.1038/emboj.2009.413

実験手法

X-RAY DIFFRACTION (1.55 Å)