SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 is a protein that in humans is encoded by the SMARCAL1gene.[1][2][3]
The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The SMARCAL1 protein convert RPA-bound, single stranded DNA into double-stranded DNA, an enzyme activity termed "annealing helicase".[4]
The encoded protein shows sequence similarity to the E. coliRNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency.[3]
Model organisms have been used in the study of SMARCAL1 function. A conditional knockout mouse line, called Smarcal1tm1a(EUCOMM)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty tests were carried out and one significant phenotype was observed: homozygous mutant mice had abnormal brain histopathology, including an enlarged hippocampus and a thickened hippocampus stratum oriens.[5]
References
↑Muthuswami R, Truman PA, Mesner LD, Hockensmith JW (Mar 2000). "A eukaryotic SWI2/SNF2 domain, an exquisite detector of double-stranded to single-stranded DNA transition elements". The Journal of Biological Chemistry. 275 (11): 7648–55. doi:10.1074/jbc.275.11.7648. PMID10713074.
↑Coleman MA, Eisen JA, Mohrenweiser HW (May 2000). "Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse". Genomics. 65 (3): 274–82. doi:10.1006/geno.2000.6174. PMID10857751.
↑ 5.05.15.2Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
Bökenkamp A, deJong M, van Wijk JA, Block D, van Hagen JM, Ludwig M (Dec 2005). "R561C missense mutation in the SMARCAL1 gene associated with mild Schimke immuno-osseous dysplasia". Pediatric Nephrology. 20 (12): 1724–8. doi:10.1007/s00467-005-2047-x. PMID16237566.
