| Structural highlights
6j0x is a 8 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 6j0w |
| Gene: | RTT107, ESC4, YHR154W (Baker's yeast), MMS22, SLM2, YLR320W (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RT107_YEAST] Required for resumption of chromosome replication after DNA damage, specifically in S phase. Is recruited to chromatin in the presence of RTT109 and RTT101 in response to stalled replication forks and acts as a scaffold during DNA repair.[1] [2] [MMS22_YEAST] Substrate targeting component of a cullin-RING-based E3 ubiquitin-protein ligase complex RTT101(MMS1-MMS22). RTT101(MMS1-MMS22) promotes fork progression through damaged DNA or natural pause sites by stabilizing replication proteins like the replication fork-pausing complex (FPC) and leading-strand polymerase at stalled replication forks. RTT101(MMS1-MMS22) ubiquitinates the acetylated histones H3K56ac-H4 at lysine residues H3K121, H3K122 and H3K125. Ubiquitination is required for efficient histone deposition during replication-coupled nucleosome assembly, probably by facilitating the transfer of H3-H4 from ASF1 to other chaperones involved in histone deposition.[3] [4] [5] [6] [7] [8] [9] [10]
Publication Abstract from PubMed
BRCT domains support myriad protein-protein interactions involved in genome maintenance. Although di-BRCT recognition of phospho-proteins is well known to support the genotoxic response, whether multi-BRCT domains can acquire distinct structures and functions is unclear. Here we present the tetra-BRCT structures from the conserved yeast protein Rtt107 in free and ligand-bound forms. The four BRCT repeats fold into a tetrahedral structure that recognizes unmodified ligands using a bi-partite mechanism, suggesting repeat origami enabling function acquisition. Functional studies show that Rtt107 binding of partner proteins of diverse activities promotes genome replication and stability in both distinct and concerted manners. A unified theme is that tetra- and di-BRCT domains of Rtt107 collaborate to recruit partner proteins to chromatin. Our work thus illustrates how a master regulator uses two types of BRCT domains to recognize distinct genome factors and direct them to chromatin for constitutive genome protection.
Molecular Basis for Control of Diverse Genome Stability Factors by the Multi-BRCT Scaffold Rtt107.,Wan B, Wu J, Meng X, Lei M, Zhao X Mol Cell. 2019 Jul 25;75(2):238-251.e5. doi: 10.1016/j.molcel.2019.05.035. Epub, 2019 Jul 16. PMID:31348879[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rouse J. Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. EMBO J. 2004 Mar 10;23(5):1188-97. Epub 2004 Feb 26. PMID:14988729 doi:http://dx.doi.org/10.1038/sj.emboj.7600129
- ↑ Roberts TM, Zaidi IW, Vaisica JA, Peter M, Brown GW. Regulation of rtt107 recruitment to stalled DNA replication forks by the cullin rtt101 and the rtt109 acetyltransferase. Mol Biol Cell. 2008 Jan;19(1):171-80. Epub 2007 Oct 31. PMID:17978089 doi:http://dx.doi.org/10.1091/mbc.E07-09-0961
- ↑ Chang M, Bellaoui M, Boone C, Brown GW. A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16934-9. Epub 2002 Dec 13. PMID:12482937 doi:10.1073/pnas.262669299
- ↑ Araki Y, Kawasaki Y, Sasanuma H, Tye BK, Sugino A. Budding yeast mcm10/dna43 mutant requires a novel repair pathway for viability. Genes Cells. 2003 May;8(5):465-80. PMID:12694535
- ↑ Baldwin EL, Berger AC, Corbett AH, Osheroff N. Mms22p protects Saccharomyces cerevisiae from DNA damage induced by topoisomerase II. Nucleic Acids Res. 2005 Feb 17;33(3):1021-30. doi: 10.1093/nar/gki246. Print, 2005. PMID:15718301 doi:http://dx.doi.org/10.1093/nar/gki246
- ↑ Archambault V, Ikui AE, Drapkin BJ, Cross FR. Disruption of mechanisms that prevent rereplication triggers a DNA damage response. Mol Cell Biol. 2005 Aug;25(15):6707-21. PMID:16024805 doi:http://dx.doi.org/25/15/6707
- ↑ Duro E, Vaisica JA, Brown GW, Rouse J. Budding yeast Mms22 and Mms1 regulate homologous recombination induced by replisome blockage. DNA Repair (Amst). 2008 May 3;7(5):811-8. doi: 10.1016/j.dnarep.2008.01.007. Epub, 2008 Mar 5. PMID:18321796 doi:http://dx.doi.org/10.1016/j.dnarep.2008.01.007
- ↑ Zaidi IW, Rabut G, Poveda A, Scheel H, Malmstrom J, Ulrich H, Hofmann K, Pasero P, Peter M, Luke B. Rtt101 and Mms1 in budding yeast form a CUL4(DDB1)-like ubiquitin ligase that promotes replication through damaged DNA. EMBO Rep. 2008 Oct;9(10):1034-40. doi: 10.1038/embor.2008.155. Epub 2008 Aug 15. PMID:18704118 doi:http://dx.doi.org/10.1038/embor.2008.155
- ↑ Vaisica JA, Baryshnikova A, Costanzo M, Boone C, Brown GW. Mms1 and Mms22 stabilize the replisome during replication stress. Mol Biol Cell. 2011 Jul 1;22(13):2396-408. doi: 10.1091/mbc.E10-10-0848. Epub, 2011 May 18. PMID:21593207 doi:http://dx.doi.org/10.1091/mbc.E10-10-0848
- ↑ Han J, Zhang H, Zhang H, Wang Z, Zhou H, Zhang Z. A Cul4 E3 ubiquitin ligase regulates histone hand-off during nucleosome assembly. Cell. 2013 Nov 7;155(4):817-29. doi: 10.1016/j.cell.2013.10.014. PMID:24209620 doi:http://dx.doi.org/10.1016/j.cell.2013.10.014
- ↑ Wan B, Wu J, Meng X, Lei M, Zhao X. Molecular Basis for Control of Diverse Genome Stability Factors by the Multi-BRCT Scaffold Rtt107. Mol Cell. 2019 Jul 25;75(2):238-251.e5. doi: 10.1016/j.molcel.2019.05.035. Epub, 2019 Jul 16. PMID:31348879 doi:http://dx.doi.org/10.1016/j.molcel.2019.05.035
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