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Cohesin complexes with a potential to link mammalian meiosis to cancer.

Strunnikov A - Cell Regen (Lond) (2013)

Bottom Line: The recent characterization of a new set of genes encoding cohesin subunits specific for meiosis in vertebrates adds several levels of complexity to the task of structure-function analysis of specific cohesin pathways, even more so in relation to their aberrant functionality in cancers.These three proteins, SMC1β, RAD21L and STAG3 are likely involved in a specific function in the first meiotic prophase, genetic recombination, and segregation of homologues.However, at present, it is rather challenging to pinpoint the molecular role of these proteins, particularly in synaptonemal complex or centromere function, due to the multiplicity of different cohesins in meiosis.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou Institutes of Biomedicine and Health, Molecular Epigenetics Laboratory, 190 Kai Yuan Avenue, Science Park, Guangzhou, 510530 China.

ABSTRACT
Among multiple genes aberrantly activated in cancers, invariably, there is a group related to the capacity of cell to self-renewal. Some of these genes are related to the normal process of development, including the establishment of a germline. This group, a part of growing family of Cancer/Testis (CT) genes, now includes the meiosis specific subunits of cohesin complex. The first reports characterizing the SMC1 and RAD21 genes, encoding subunits of cohesin, were published 20 years ago; however the exact molecular mechanics of cohesin molecular machine in vivo remains rather obscure notwithstanding ample elegant experiments. The matters are complicated by the fact that the evolution of cohesin function, which is served by just two basic types of protein complexes in budding yeast, took an explosive turn in Metazoa. The recent characterization of a new set of genes encoding cohesin subunits specific for meiosis in vertebrates adds several levels of complexity to the task of structure-function analysis of specific cohesin pathways, even more so in relation to their aberrant functionality in cancers. These three proteins, SMC1β, RAD21L and STAG3 are likely involved in a specific function in the first meiotic prophase, genetic recombination, and segregation of homologues. However, at present, it is rather challenging to pinpoint the molecular role of these proteins, particularly in synaptonemal complex or centromere function, due to the multiplicity of different cohesins in meiosis. The roles of these proteins in cancer cell physiology, upon their aberrant activation in tumors, also remain to be elucidated. Nevertheless, as the existence of Cancer/Testis cohesin complexes in tumor cells appears to be all but certain, this brings a promise of a new target for cancer therapy and/or diagnostics.

No MeSH data available.


Related in: MedlinePlus

Cohesin complexes based on all possible combinations of known cohesin subunits. Meiosis-specific complexes are boxed in blue, and mitotic, which are also found in meiosis, are boxed in red. The complexes that were not validated biochemically are shown shaded. (*) Interaction of REC8 with SA/STAG subunits has not been studied exhaustively in mammalian systems.
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Fig1: Cohesin complexes based on all possible combinations of known cohesin subunits. Meiosis-specific complexes are boxed in blue, and mitotic, which are also found in meiosis, are boxed in red. The complexes that were not validated biochemically are shown shaded. (*) Interaction of REC8 with SA/STAG subunits has not been studied exhaustively in mammalian systems.

Mentions: Making the sense of the multitude of cohesin subunits is becoming objectively more and more difficult. Recently, three groups characterized the RAD21L (RAD21-like) protein, which is yet another meiosis-specific cohesin subunit [31–33]. RAD21L is expressed strictly in germline, i.e. in spermatocytes and oocytes. The presence of putative RAD21L complexes in the repertoire of meiotic cohesins significantly increases the level of potential complexity in the task of defining separate types of cohesin complexes in meiosis. A recent review on the subject estimates that there are 18 potential cohesin complexes (Figure 1) that could be present in cells, based on purely combinatorial considerations [34]. However, RAD21L cohesin complexes appear to come in only two forms in vivo: with SMC3 and STAG3 complexed with either SMC1α or SMC1β [31, 35, 36].Figure 1


Cohesin complexes with a potential to link mammalian meiosis to cancer.

Strunnikov A - Cell Regen (Lond) (2013)

Cohesin complexes based on all possible combinations of known cohesin subunits. Meiosis-specific complexes are boxed in blue, and mitotic, which are also found in meiosis, are boxed in red. The complexes that were not validated biochemically are shown shaded. (*) Interaction of REC8 with SA/STAG subunits has not been studied exhaustively in mammalian systems.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230521&req=5

Fig1: Cohesin complexes based on all possible combinations of known cohesin subunits. Meiosis-specific complexes are boxed in blue, and mitotic, which are also found in meiosis, are boxed in red. The complexes that were not validated biochemically are shown shaded. (*) Interaction of REC8 with SA/STAG subunits has not been studied exhaustively in mammalian systems.
Mentions: Making the sense of the multitude of cohesin subunits is becoming objectively more and more difficult. Recently, three groups characterized the RAD21L (RAD21-like) protein, which is yet another meiosis-specific cohesin subunit [31–33]. RAD21L is expressed strictly in germline, i.e. in spermatocytes and oocytes. The presence of putative RAD21L complexes in the repertoire of meiotic cohesins significantly increases the level of potential complexity in the task of defining separate types of cohesin complexes in meiosis. A recent review on the subject estimates that there are 18 potential cohesin complexes (Figure 1) that could be present in cells, based on purely combinatorial considerations [34]. However, RAD21L cohesin complexes appear to come in only two forms in vivo: with SMC3 and STAG3 complexed with either SMC1α or SMC1β [31, 35, 36].Figure 1

Bottom Line: The recent characterization of a new set of genes encoding cohesin subunits specific for meiosis in vertebrates adds several levels of complexity to the task of structure-function analysis of specific cohesin pathways, even more so in relation to their aberrant functionality in cancers.These three proteins, SMC1β, RAD21L and STAG3 are likely involved in a specific function in the first meiotic prophase, genetic recombination, and segregation of homologues.However, at present, it is rather challenging to pinpoint the molecular role of these proteins, particularly in synaptonemal complex or centromere function, due to the multiplicity of different cohesins in meiosis.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou Institutes of Biomedicine and Health, Molecular Epigenetics Laboratory, 190 Kai Yuan Avenue, Science Park, Guangzhou, 510530 China.

ABSTRACT
Among multiple genes aberrantly activated in cancers, invariably, there is a group related to the capacity of cell to self-renewal. Some of these genes are related to the normal process of development, including the establishment of a germline. This group, a part of growing family of Cancer/Testis (CT) genes, now includes the meiosis specific subunits of cohesin complex. The first reports characterizing the SMC1 and RAD21 genes, encoding subunits of cohesin, were published 20 years ago; however the exact molecular mechanics of cohesin molecular machine in vivo remains rather obscure notwithstanding ample elegant experiments. The matters are complicated by the fact that the evolution of cohesin function, which is served by just two basic types of protein complexes in budding yeast, took an explosive turn in Metazoa. The recent characterization of a new set of genes encoding cohesin subunits specific for meiosis in vertebrates adds several levels of complexity to the task of structure-function analysis of specific cohesin pathways, even more so in relation to their aberrant functionality in cancers. These three proteins, SMC1β, RAD21L and STAG3 are likely involved in a specific function in the first meiotic prophase, genetic recombination, and segregation of homologues. However, at present, it is rather challenging to pinpoint the molecular role of these proteins, particularly in synaptonemal complex or centromere function, due to the multiplicity of different cohesins in meiosis. The roles of these proteins in cancer cell physiology, upon their aberrant activation in tumors, also remain to be elucidated. Nevertheless, as the existence of Cancer/Testis cohesin complexes in tumor cells appears to be all but certain, this brings a promise of a new target for cancer therapy and/or diagnostics.

No MeSH data available.


Related in: MedlinePlus