2wd5
SMC hinge heterodimer (Mouse)SMC hinge heterodimer (Mouse)
Structural highlights
FunctionSMC1A_MOUSE Involved in chromosome cohesion during cell cycle and in DNA repair. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, and works as a downstream effector in the ATM/NBS1 branch of S-phase checkpoint (By similarity). Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint. 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 PubMedCohesin's structural maintenance of chromosome 1 (Smc1) and Smc3 are rod-shaped proteins with 50-nm long intra-molecular coiled-coil arms with a heterodimerization domain at one end and an ABC-like nucleotide-binding domain (NBD) at the other. Heterodimerization creates V-shaped molecules with a hinge at their centre. Inter-connection of NBDs by Scc1 creates a tripartite ring within which, it is proposed, sister DNAs are entrapped. To investigate whether cohesin's hinge functions as a possible DNA entry gate, we solved the crystal structure of the hinge from Mus musculus, which like its bacterial counterpart is characterized by a pseudo symmetric heterodimeric torus containing a small channel that is positively charged. Mutations in yeast Smc1 and Smc3 that together neutralize the channel's charge have little effect on dimerization or association with chromosomes, but are nevertheless lethal. Our finding that neutralization reduces acetylation of Smc3, which normally occurs during replication and is essential for cohesion, suggests that the positively charged channel is involved in a major conformational change during S phase. A positively charged channel within the Smc1/Smc3 hinge required for sister chromatid cohesion.,Kurze A, Michie KA, Dixon SE, Mishra A, Itoh T, Khalid S, Strmecki L, Shirahige K, Haering CH, Lowe J, Nasmyth K EMBO J. 2011 Jan 19;30(2):364-78. Epub 2010 Dec 7. PMID:21139566[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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