SMARCAD1 Gene

SMARCAD1 (SMARCAD1 is the acronym for SWI/SNF-Related, Matrix-Associated Actin-Dependent Regulator Of Chromatin, Subfamily A, Containing DEAD/H Box 1) is a protein-coding gene located on chromosome 4q22.3 b. The SMARCAD1 gene encodes a member of the SNF subfamily of helicase proteins. The encoded protein plays a critical role in the restoration of heterochromatin organization and the propagation of epigenetic patterns after DNA replication by mediating histone H3/H4 deacetylation.

Diseases associated with SMARCAD1 include:

• Vein dermatoglyphics, isolated congenital (mutation in SMARCAD1; disorder in which affected individuals lack papillary ridges on the palms of the hands and soles of the feet as an isolated symptom, leaving no fingerprints).
• Absent dermatoglyphic congenital milia syndrome with mutation in SMARCAD1 (Basan syndrome). Variant of isolated congenital vein dermatoglyphia syndrome.
• Diffuse palmoplantar atatosis with sclerodactyly and increased risk of spinocellular carcinoma with mutation in SMARCAD1 (Huriez syndrome ).

Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Biological functions of the gene include nucleic acid binding and helicase activity. An important paralog of this gene is HELLS.

The DNA helicase that has intrinsic ATP-dependent nucleosome remodeling activity and is required for both DNA repair and heterochromatin organization. Promotes resection of the DNA end of double-strand breaks (DSBs) after DNA damage: likely acts by weakening histone-DNA interactions in nucleosomes flanking DSBs. Required for restoration of heterochromatin organization after replication. Acts at replication sites to facilitate maintenance of heterochromatin by directing deacetylation of H3 and H4 histones, H3-'Lys-9' trimethylation (H3K9me3), and restoration of silencing.

DNA is packaged into highly condensed chromatin in eukaryotes for organization of the genome. Access to DNA within nucleosomes is required for a variety of biological processes in cells. These include transcription, replication and DNA repair. To accomplish this, cells employ a series of specialized ATP-dependent chromatin remodeling protein complexes that provide dynamic access to packaged DNA. SMARCAD1, a DEAD/H-box-containing helicase, is one such chromatin remodeler that has been shown to play a key role in several cellular processes (Tong ZB et al. 2020).

SMARCAD1 is thought to play a role in carcinoma (e.g. breast cancer) metastasis (Al Kubaisy E et al. 2016).

1. Adra C et al. (2000) SMARCAD1, a novel human helicase family-defining member associated with genetic instability: cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases. Genomics 69: 162-173.
2. Ai H et al. (2019) Examination of the deubiquitylation site selectivity of USP51 by using chemically synthesized ubiquitylated histones. ChemBioChem 20: 221-229.
3. Al Kubaisy E et al. (2016) SMARCAD1 knockdown uncovers its role in breast cancer cell migration, invasion, and metastasis. Expert Opin Ther Targets 20:1035-1043.
4. Tong ZB et al. (2020) The mechanism of chromatin remodeler SMARCAD1/Fun30 in response to DNA damage. Front Cell Dev Biol 8:560098.