SMCs
Structural maintenance of chromosomes proteins (SMCs) are chromosomal ATPases, highly conserved from bacteria to humans, that play fundamental roles in many aspects of higher-order chromosome organization and dynamics.
Members
| SMC1A | SMC1B | SMC2 | SMC3 | SMC4 | SMC5 | SMC6 |
Of the three structural maintenance of chromosome (SMC) complexes, two directly regulate chromosome dynamics. The third, Smc5/6, functions mainly in homologous recombination and in completing DNA replication.
Smc5/6 coordinates DNA repair, in part through post-translational modification of uncharacterized target proteins that can dictate their subcellular localization, and that Smc5/6 also functions to establish DNA-damage-dependent cohesion.
A nucleolar-specific Smc5/6 function has been proposed because Smc5/6 yeast mutants display penetrant phenotypes of ribosomal DNA (rDNA) instability. rDNA repeats are replicated unidirectionally.
In eukaryotes, SMC1 and SMC3 act as the core of the cohesin complexes that mediate sister chromatid cohesion, whereas SMC2 and SMC4 function as the core of the condensin complexes that are essential for chromosome assembly and segregation.
Another complex containing SMC5 and SMC6 (Smc5/6) is implicated in DNA repair and checkpoint responses.
The SMC complexes form unique ring- or V-shaped structures with long coiled-coil arms, and function as ATP-modulated, dynamic molecular linkers of the genome.
Structural maintenance of chromosomes (SMC) proteins are ubiquitous in organisms from bacteria to humans, and function as core components of the condensin and cohesin complexes in eukaryotes.
SMC proteins adopt a V-shaped structure with two long arms, each of which has an ATP-binding head domain at the distal end.
These uniquely designed protein machines interact with DNA strands and such interactions are modulated by the ATP-binding and -hydrolysis cycle.
SMC proteins use a diverse array of intramolecular and intermolecular protein-protein interactions to actively fold, tether and manipulate DNA strands.
Pathology
Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation (#17273969#)
References
Murray JM, Carr AM. Smc5/6: a link between DNA repair and unidirectional replication? Nat Rev Mol Cell Biol. 2007 Dec 5; PMID: #18059412#
Deardorff MA, Kaur M, Yaeger D, Rampuria A, Korolev S, Pie J, Gil-Rodriguez C, Arnedo M, Loeys B, Kline AD, Wilson M, Lillquist K, Siu V, Ramos FJ, Musio A, Jackson LS, Dorsett D, Krantz ID. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am J Hum Genet. 2007 Mar;80(3):485-94. PMID: #17273969#
Hirano T. At the heart of the chromosome: SMC proteins in action. Nat Rev Mol Cell Biol. 2006 May;7(5):311-22. PMID: #16633335#
Losada A, Hirano T. Dynamic molecular linkers of the genome: the first decade of SMC proteins. Genes Dev. 2005 Jun 1;19(11):1269-87. PMID: #15937217#