SMC1
Overview
Structural Maintenance of Chromosomes 1 (SMC1) is a protein that in humans is encoded by the SMC1A gene. It is a member of the Structural Maintenance of Chromosomes (SMC) protein family, which is involved in a range of cellular processes including chromosome condensation, segregation, DNA repair, and regulation of gene expression.
Function
SMC1 is a core component of the cohesin complex, which is responsible for the cohesion of sister chromatids during cell division. This complex also plays a role in DNA repair and the regulation of gene expression. The cohesin complex is composed of four core proteins: SMC1, SMC3, RAD21, and either STAG1 or STAG2. SMC1 and SMC3 form a heterodimeric ring structure that entraps sister chromatids, while RAD21 and STAG proteins stabilize the ring.
Structure
SMC1, like other SMC proteins, has a unique structure consisting of five domains: two terminal globular domains, two coiled-coil regions, and a central hinge domain. The N- and C-terminal globular domains contain Walker A and Walker B motifs, which are characteristic of ATPases. The coiled-coil regions facilitate the dimerization of SMC1 with SMC3, while the hinge domain allows for the opening and closing of the SMC ring.
Clinical Significance
Mutations in the SMC1A gene can lead to a variety of human diseases. For instance, they are associated with Cornelia de Lange Syndrome (CdLS), a rare genetic disorder characterized by growth retardation, intellectual disability, and distinctive facial features. SMC1A mutations have also been implicated in certain types of cancer, including breast and ovarian cancer.
Research
Research on SMC1 has provided valuable insights into the mechanisms of chromosome segregation and cohesion. It has also shed light on the molecular basis of CdLS and other diseases associated with cohesin dysfunction. Current research is focused on understanding the role of SMC1 in DNA repair and gene regulation, as well as developing therapeutic strategies for diseases associated with SMC1A mutations.
See Also
