3L40

Crystal Structure of S. pombe Brc1 BRCT5-BRCT6 domains

Summary for 3L40

• Entry DOI: 10.2210/pdb3l40/pdb
• Related: 1jnx 1t2v 2azm 2r1z 3hue 3L41
• Descriptor: BRCT-containing protein 1 (2 entities in total)
• Functional Keywords: brc1, brct domain, tandem brct repeat, phosphoserine binding domain, dna repair, cell division, mitosis, cell cycle
• Biological source: Schizosaccharomyces pombe (Fission yeast)
• Total number of polymer chains: 2
• Total formula weight: 49650.79

Authors

Williams, R.S.,Williams, J.S.,Guenther, G.,Tainer, J.A. (deposition date: 2009-12-18, release date: 2010-02-09, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.55 Å)