Structural highlights
3l40 is a 2 chain structure with sequence from Cbs 356. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Related: | 1jnx, 3hue, 2r1z, 1t2v, 2azm, 3l41 |
| Gene: | brc1, SPBC582.05c (CBS 356) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[BRC1_SCHPO] Required for mitotic fidelity, specifically in the G2 phase of the cell cycle. Plays a role in chromatin organization.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
gammaH2A binds Brc1 to maintain genome integrity during S-phase.,Williams JS, Williams RS, Dovey CL, Guenther G, Tainer JA, Russell P EMBO J. 2010 Mar 17;29(6):1136-48. Epub 2010 Jan 21. PMID:20094029[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Williams JS, Williams RS, Dovey CL, Guenther G, Tainer JA, Russell P. gammaH2A binds Brc1 to maintain genome integrity during S-phase. EMBO J. 2010 Mar 17;29(6):1136-48. Epub 2010 Jan 21. PMID:20094029 doi:10.1038/emboj.2009.413
