Shugoshin 1 or Shugoshin-like 1, is a
protein that in humans is encoded by the ''SGO1''
gene.
Model organisms
Model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
s have been used in the study of SGOL1 function. A conditional
knockout mouse line, called ''Sgol1
tm1a(EUCOMM)Wtsi''
has been generated.
Male and female animals underwent a standardized
phenotypic screen to determine the effects of deletion.
Twenty six tests were carried out on
mutant mice and three significant abnormalities were observed. No
homozygous mutant embryos were identified during gestation, and thus none survived until
weaning. The remaining tests were carried out on
heterozygous mutant adult mice and a decreased regulatory
T cell number was observed in male animals.
Mechanisms
A physical mechanism that guarantees the accurate segregation of
sister chromatids during
mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
arises from the ring shaped
cohesin complex consisting of 4 subunits (
SMC1A/
B,
SMC3,
SCC1, and
SA1/
2 in humans). This complex encircles the two sister chromatids and resists the pulling force of
microtubules. The characteristic X-shape chromosomes are formed due to the
centromeric
The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers ...
cohesin protected by Shugoshin-
PP2A
Protein phosphatase 2 (PP2), also known as PP2A, is an enzyme that in humans is encoded by the ''PPP2CA'' gene. The PP2A heterotrimeric protein phosphatase is ubiquitously expressed, accounting for a large fraction of phosphatase activity in ...
complex.
Kinetochore
A kinetochore (, ) is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere ...
localization of Sgo1-PP2A is dependent upon phosphorylation on
histone H2A
Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells.
The other histone proteins are: H1, H2B, H3 and H4.
Background
Histones are proteins that package DNA into nucleosomes. Hi ...
of
nucleosome
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamen ...
, which is the important substrate of spindle checkpoint kinase
BUB1
Mitotic checkpoint serine/threonine-protein kinase BUB1 also known as BUB1 (budding uninhibited by benzimidazoles 1) is an enzyme that in humans is encoded by the ''BUB1'' gene.
Bub1 is a serine/threonine protein kinase first identified in geneti ...
. Centromeric cohesin and H2A-pT120 specify two distinct pools of Sgo1-PP2A at inner centromeres and kinetochores respectively, while the
CDK1
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in t ...
/cyclin B phosphorylation on Sgo1 is essential for Sgo1-PP2A to protect centromeric cohesin, not only for bringing PP2A to cohesin, but also physically shield out the negative regulator
WAPAL from cohesin.
References
Further reading
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{{refend
Genes mutated in mice