The protein encoded by the Ccc1 gene is a member of the coiled-coil (CC) family of proteins. CC proteins are characterized by a long, alpha helical coil domain that mediates protein-protein interactions. Ccc1 is thought to be involved in the maintenance of chromosome stability. Mutations in this gene have been associated with autosomal recessive congenital cataract 1 (CATCT1), also known as Goudie-White syndrome 3 (GW3). This condition is characterized by cataracts, microcornea, and other ocular abnormalities.
Ccc1 was first identified as a putative human homolog of the Saccharomyces cerevisiae SGS1 gene (also known as CDC45) . SGS1 is a member of the RecQ helicase family and functions in DNA replication and repair. The sequence similarity between Ccc1 and SGS1 suggests that Ccc1 may also play a role in these processes. However, the precise function of Ccc1 remains unknown.
Ccc1 is widely expressed throughout the body, with highest levels in brain, kidney, heart, and skeletal muscle . In addition to its role in CATCT1/GW3, mutations in this gene have also been associated with nonsyndromic autosomal recessive congenital cataract 2 (NSAC2). NSAC2 is an isolated form of congenital cataract that does not involve any other ocular or systemic abnormalities.
The structure of Ccc1 consists of two coiled-coil domains connected by a flexible linker region . The N-terminal domain contains an ATPase activity that is required for DNA binding . The C-terminal domain contains the helicase activity responsible for unwinding double stranded DNA . Both domains are necessary for full activity of the protein.
Mutations in the CCCAAT motif within exon 4 of the CCCAAT box have been shown to result in GW3/CATCT1 . These mutations lead to decreased DNA binding affinity and reduced helicase activity . As a result, cells are unable to properly maintain genomic stability , leading to increased susceptibility to chromosome breakage and instability .