- Two proteins have been found to
mediate chromosome organization.
- This could aid in the
identification of the origins of cancer.
The DNA in our
body is tightly packed and if opened and stretched out, it will extend to about
6 feet. There are changes that occur in a chromosome to aid in better
expression and for maintaining the genome.
the Structural Maintenance of Chromosome Protein (SMC) are responsible for
mediating these changes in the chromosome.
- The changes in the chromosome are
mediated in part by promoting the interaction with certain sites on the
chromosomes while inhibiting certain other sites.
- The SMC proteins use energy from
ATP to make the changes to the chromosome.
important structural maintenance proteins that play an important role in
mediating changes in the chromosome structure.
‘Two proteins hold the key to chromosome organization and genetic data preservation.’
Role of SMC
in Genome Organization
process of transcription and repair of DNA, there are interactions with distant
parts of the DNA that occur. The DNA is organized into loops during this stage
and these structures are stabilized by these proteins.
mark boundaries in the one dimensional DNA strand while these domains are
arranged in the nucleus in a 3 dimensional space. Apart from this, the proteins
also prevent association between homologous regions.
Role of SMC
in Expression of Genes
Studies on Caenorhabditis
have shown that SMC play an important role in gene expression. C.
has a protein that is similar to condensin but differs in one
single subunit, SMC-4 is changed to DPY 27. The protein is called Dosage
Compensation Complex (DCC). The binding of DCC to specific sites on the
promoter correlates with the expression levels of the gene.
entire length of the genome of C. elegans,
DCC was found to bind to
promoters of genes that were highly expressed.
Role of SMC
in Metazoan Development
There has been
increasing evidence that points towards the role of SMC in development
processes that include
- Neuronal development
- Cell fate patterning
disorder in humans called Cornelia de lange
is caused due to heterozygous
mutations in the subunits of condensin.
Role of SMC
in Loading and Distribution
Sites that are
enriched with cohesin occur every 15Kb, with the distribution of the cohesin
rich sites being dynamic on the chromosome. The cohesin rich sites are
influenced by DNA repair and translation.
Condensin is an
important factor in DNA loading with the existence of two condensin complexes.
SMC, both condensin and cohesin have interchangeable molecular parts that can
be reshuffled. These create independent complexes that have their distinct
function. When even one cohesin subunit is changed, it leads to a dramatic
change in function of the complex.
The SMC complex
with its interchangeable subunits may be specified after post-translational
modifications. Studies so far have not been able to clearly define the
functions of SMC but it has been found that disruption of the subunit can lead
to mitotic defects as well as lethality.
Greater Insights into
the Function of SMC
A new study by
Ken-ichi Noma and colleagues has provided greater insight into how these two
proteins play an important role in organization of chromosomes in our genome.
who is the lead author of the study and is an associate professor at The Wistar
Institute in the department of gene expression and regulation program says
"Understanding the three-dimensional structure of our genome is critical if we
are to properly understand key functions like transcription, DNA replication
undergoes cell division that is similar to humans and so was used to study the
exact roles of cohesin and condensin in the organization of DNA. The studies
showed that the two SMC proteins bind to the same regions of the DNA but the
domain vary in function and size depending on the protein that binds to them.
Result of the
- The association between closely
placed chromatin are mediated by cohesin.
- Larger associations are mediated
The domains that
the proteins bind to play a very important role in ensuring that cells carry
out their tasks. If any of the SMC proteins do not bind well, it can lead to a
host of diseases that include cancer.
induced a mutation in ace2Δ gene which codes for transcription factors that are
associated with condensation. This led to disruption of the domains that the
genes were associated with and further led to defects in chromosome
suggest that the transcription factors play an important role in binding the
condensin to the chromosomes which then regulate cell division or mitosis. Only
when this process takes place does chromosome segregation occur.
Noma adds "The
more we know about the role of condensin and cohesin, the more we can learn
about key processes involved in the cell cycle and how cancer can be controlled
through processes like cellular senescence."
understanding of the roles and function of condensin and cohesin in chromosome
organization aid in better understanding of the mechanism involved. This will
aid in analyzing genetic
- Condensin and cohesin complexity: the expanding repertoire of functions - (https://mcb.berkeley.edu/labs/meyer/publicationpdfs/WoodSeverson.pdf)