Cohesin subunit SA-2 (SA2) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''STAG2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
SA2 is a subunit of the
Cohesin
Cohesin is a protein complex that mediates Establishment of sister chromatid cohesion, sister chromatid cohesion, homologous recombination, and Topologically associating domain, DNA looping. Cohesin is formed of SMC3, SMC1A, SMC1, RAD21, SCC1 an ...
complex which mediates
sister chromatid cohesion,
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
and
DNA looping. In somatic cells cohesin is formed of
SMC3,
SMC1,
RAD21
Double-strand-break repair protein rad21 homolog is a protein that in humans is encoded by the ''RAD21'' gene. ''RAD21'' (also known as ''Mcd1'', ''Scc1'', ''KIAA0078'', ''NXP1'', ''HR21''), an essential gene, encodes a DNA repair#Double-strand b ...
and either
SA1 or SA2 whereas in
meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
, cohesin is formed of SMC3,
SMC1B,
REC8 and
SA3.
''STAG2'' is frequently mutated in a range of cancers and several other disorders.
Function
SA2 is part of the
cohesin complex, which is a structure that holds the sister
chromatid
A chromatid (Greek ''khrÅmat-'' 'color' + ''-id'') is one half of a duplicated chromosome. Before replication, one chromosome is composed of one DNA molecule. In replication, the DNA molecule is copied, and the two molecules are known as chrom ...
s together after
DNA replication
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...
. STAG2 has been shown to
interact with
STAG1.
Cohesion folds by DNA loop extrusion and this cohesion consists of SMC1, SMC3, RAD21, and either STAG1 or STAG2.
SA2 interacts with a ring-like structure composed of SMC1A, SMC3, and RAD21, to form the core of the cohesin complex. The ring-like structure binds chromosomes together until degradation of the cohesin complex is finished during cell division.
This allows for the replicated chromosomes to separate into two new cells. Another role of ''STAG2'' is to encode the stromal antigen 2 protein, which is involved in chromatin organization'','' transcription, DNA repair and control of downstream gene expression.
Structure
Of the cohesin complex, ''STAG2'' is the subunit where the most variants have been reported in cancer. This is thought to be because this gene is located in the
X chromosome
The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...
, therefore only one mutation is needed to inactivate it
Xq25 duplication syndrome is an X-linked neurodevelopmental disorder that results in delayed development and intellectual disability associated with abnormal behavior and dysmorphic facial features, and the whole STAG2 gene can develop ''STAG2''
encephalopathy
Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...
. This has all the symptoms of epilepsy wit
eyelid myoclonia and absences(EMA), and was formally named Jeavons syndrome (JS).
Mutations
One result of mutations in ''STAG2'' can result in one third of non-muscle-invasive bladder cancer to have complete loss of SA2 protein.
The loss of this protein has been shown to indicate the prognosis of disease and survival. it has been shown there was a delay in maturation of oligodendrocytes and transcription of myelination-related genes was reduced. Cohesion is needed in proper gene expression in specific cells and an implication the myelination is affected in a negative way.
Mutations of STAG2 occur frequently in many cancers, which indicates this protein has a role in cancer. Mutations of the ''STAG2'' gene are frequently seen in multiple adult and pediatric cancers. ''STAG'' has been found to be the only gene of 12 that is mutated significantly in at least four types of cancers.
References
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