SMC1B

SMC1B
Identifiers
Aliases	SMC1B , SMC1BETA, SMC1L2, structural maintenance of chromosomes 1B
External IDs	OMIM: 608685 MGI: 2154049 HomoloGene: 13786 GeneCards: SMC1B
Gene location (Human)
Chr.	Chromosome 22 (human)
End	45,413,619 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	85,016,165 bp
RNA expression pattern
	Top expressed in
	monocyte; ; Achilles tendon; ; lymph node; ; thymus; ; appendix; ; gallbladder; ; blood; ; placenta; ; smooth muscle tissue; ; gastrocnemius muscle;
	Top expressed in
	spermatid; ; spermatocyte; ; seminiferous tubule; ; secondary oocyte; ; morula; ; ovary; ; blastocyst; ; liver; ; spleen; ; jejunum;
	More reference expression data
	n/a
Gene ontology
Molecular function	DNA binding ; nucleotide binding ; ATP binding ;
Cellular component	lateral element ; condensed nuclear chromosome ; synaptonemal complex ; chromosome, centromeric region ; nucleus ; nucleoplasm ; chromosome ; meiotic cohesin complex ; cytosol ;
Biological process	cell cycle ; meiosis ; chromosome organization ; sister chromatid cohesion ;
	Sources:Amigo / QuickGO
Orthologs
	27127
	140557
	ENSG00000077935
	ENSMUSG00000022432
	Q8NDV3
	Q920F6
	NM_001291501 ; NM_148674
	NM_080470
	NP_001278430 ; NP_683515
	NP_536718
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 21, 2024

Structural maintenance of chromosomes protein 1B (SMC-1B) is a protein that in humans is encoded by the SMC1B gene.^[5]^[6]^[7] SMC proteins engage in chromosome organization and can be broken into 3 groups based on function which are cohesins, condensins, and DNA repair.^[8]^[9]^[10] SMC-1B belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis.^[7]^[11] SMC1B protein appears to participate with other cohesins REC8, STAG3 and SMC3 in sister-chromatid cohesion throughout the whole meiotic process in human oocytes.^[12]

Function

SMC1B is essential for meiosis in which it has 3 main roles.^[13] SMC1B is known to be involved in the fusion of chromosomes during meiosis in both homologous and non-homologous chromosomes.^[13] SMC1B develops the axial elements (AE) found in synaptonemal complexes in association with other cohesin proteins REC8 and SMC3 as well as AE proteins SCP2 and SCP3.^[14]^[15] Sister chromatid cohesion in meiosis is supplied by SMC1B.^[13] SMC1B can also protect telomeres from damage, something that SMC1A has not been shown to be capable of.^[16] Additionally, in somatic cells SMC1B associates with SMC3 and RAD21 in a mitotic cohesin complex which had been thought to only include SMC1α.^[17]^[18] Depletion of SMC1B in somatic cells showed dysregulation of some gene expression.^[17]

Clinical Significance

Human Papillomavirus (HPV)

Human Papillomavirus (HPV) is a DNA virus and the most prevalent sexually transmitted infection.^[19] HPV-16 and HPV-18 are responsible for most cases of cervical cancer from HPV.^[20] SMC1B has increased expression in HPV(+) cases.^[21] HPV recruits SMC1 along with a transcriptional factor, CTCF, to enable replication of the virus's genome. SMC1 is crucially important to the regulation of the virus life cycle.^[20]

Genome Instability and Cancer

SMC1B protects genetic stability from ultraviolet and infrared radiation.^[18] Altered expression of SMC1B can cause DNA damage repair to fail that then causes genome instability.^[18] Expression of SMC1B higher or lower than normal is associated with certain cancers. Meiotic subunits STAG3 and REC8 are also expressed with SMC1B in cancers.^[22] High expression of SMC1B can be associated with pancreatic cancers and ovarian cancer, while low expression increases the risk of cancer progression due to low genetic stability.^[18]

Related Research Articles

Meiosis is a special type of cell division of germ cells and apicomplexans in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and a female will fuse to create a cell with two copies of each chromosome again, the zygote.

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis. Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy).

Synapsis is the pairing of two chromosomes that occurs during meiosis. It allows matching-up of homologous pairs prior to their segregation, and possible chromosomal crossover between them. Synapsis takes place during prophase I of meiosis. When homologous chromosomes synapse, their ends are first attached to the nuclear envelope. These end-membrane complexes then migrate, assisted by the extranuclear cytoskeleton, until matching ends have been paired. Then the intervening regions of the chromosome are brought together, and may be connected by a protein-RNA complex called the synaptonemal complex. During synapsis, autosomes are held together by the synaptonemal complex along their whole length, whereas for sex chromosomes, this only takes place at one end of each chromosome.

SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes.

<span class="mw-page-title-main">Cohesin</span> Protein complex that regulates the separation of sister chromatids during cell division

Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3. Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB.

Structural maintenance of chromosomes protein 1A (SMC1A) is a protein that in humans is encoded by the SMC1A gene. SMC1A is a subunit of the cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells, cohesin is formed of SMC1A, SMC3, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3.

Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregation process occurs during both mitosis and meiosis. Chromosome segregation also occurs in prokaryotes. However, in contrast to eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation occurs progressively following replication.

Double-strand-break repair protein rad21 homolog is a protein that in humans is encoded by the RAD21 gene. RAD21, an essential gene, encodes a DNA double-strand break (DSB) repair protein that is evolutionarily conserved in all eukaryotes from budding yeast to humans. RAD21 protein is a structural component of the highly conserved cohesin complex consisting of RAD21, SMC1A, SMC3, and SCC3 [ STAG1 (SA1) and STAG2 (SA2) in multicellular organisms] proteins, involved in sister chromatid cohesion.

Structural maintenance of chromosomes protein 3 (SMC3) is a protein that in humans is encoded by the SMC3 gene. SMC3 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. In humans, SMC3 is present in all cohesin complexes whereas there are multiple paralogs for the other subunits.

Cohesin subunit SA-2 (SA2) is a protein that in humans is encoded by the STAG2 gene. SA2 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3.

Wings apart-like protein homolog (WAPL) is a protein that in humans is encoded by the WAPAL gene. WAPL is a key regulator of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. Cohesin has a ring-like arrangement and it is thought that it associates with the chromosome by entrapping it whether as a loop of DNA, a single strand or a pair of sister chromosomes. WAPL forms a complex with PDS5A or PDS5B and releases cohesin from DNA by opening the interface between SMC3 and RAD21.

Structural maintenance of chromosomes protein 6 is a protein that in humans is encoded by the SMC6 gene.

Shugoshin 2(Shugoshin-2), also known as Shugoshin-like 2, is a protein which in humans is encoded by the SGO2 gene.

Sister chromatid cohesion protein PDS5 homolog B(PDS5B) is a protein that in humans is encoded by the PDS5B gene. It is a regulatory subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. The core cohesin complex is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. PDS5 associates with WAPL to stimulate the release of cohesin from DNA but during DNA replication PDS5 promotes acetylation of SMC3 by ESCO1 and ESCO2.

Structural maintenance of chromosomes protein 5 is a protein encoded by the SMC5 gene in human.

Meiotic recombination protein REC8 homolog is a protein that in humans is encoded by the REC8 gene.

Cohesin subunit SA-1 (SA1) is a protein that in humans is encoded by the STAG1 gene. SA1 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3. There is a nonprofit community formed for those with a STAG1 Gene mutation at www.stag1gene.org.

In cell biology, Meiomitosis is an aberrant cellular division pathway that combines normal mitosis pathways with ectopically expressed meiotic machinery resulting in genomic instability.

Sister chromatid cohesion refers to the process by which sister chromatids are paired and held together during certain phases of the cell cycle. Establishment of sister chromatid cohesion is the process by which chromatin-associated cohesin protein becomes competent to physically bind together the sister chromatids. In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis. Some studies have suggested that cohesion aids in aligning the kinetochores during mitosis by forcing the kinetochores to face opposite cell poles.

Stromal antigen 3 is a protein that in humans is encoded by the STAG3 gene. STAG3 protein is a component of a cohesin complex that regulates the separation of sister chromatids specifically during meiosis. STAG3 appears to be paramount in sister-chromatid cohesion throughout the meiotic process in human oocytes and spermatocytes.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000077935 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022432 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Entrez Gene: structural maintenance of chromosomes 1B".
↑ Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, et al. (December 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–495. Bibcode:1999Natur.402..489D. doi: 10.1038/990031 . PMID 10591208.
1 2 Revenkova E, Eijpe M, Heyting C, Gross B, Jessberger R (October 2001). "Novel meiosis-specific isoform of mammalian SMC1". Molecular and Cellular Biology. 21 (20): 6984–6998. doi:10.1128/MCB.21.20.6984-6998.2001. PMC 99874 . PMID 11564881.
↑ Michaelis C, Ciosk R, Nasmyth K (October 1997). "Cohesins: chromosomal proteins that prevent premature separation of sister chromatids". Cell. 91 (1): 35–45. doi: 10.1016/S0092-8674(01)80007-6 . PMID 9335333. S2CID 18572651.
↑ Hirano T, Kobayashi R, Hirano M (May 1997). "Condensins, chromosome condensation protein complexes containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein". Cell. 89 (4): 511–521. doi: 10.1016/S0092-8674(00)80233-0 . PMID 9160743. S2CID 15061740.
↑ Fousteri MI, Lehmann AR (April 2000). "A novel SMC protein complex in Schizosaccharomyces pombe contains the Rad18 DNA repair protein". The EMBO Journal. 19 (7): 1691–1702. doi:10.1093/emboj/19.7.1691. PMC 310237 . PMID 10747036.
↑ Mannini L, Cucco F, Quarantotti V, Amato C, Tinti M, Tana L, et al. (December 2015). "SMC1B is present in mammalian somatic cells and interacts with mitotic cohesin proteins". Scientific Reports. 5: 18472. Bibcode:2015NatSR...518472M. doi:10.1038/srep18472. PMC 4682075 . PMID 26673124.
↑ Garcia-Cruz R, Brieño MA, Roig I, Grossmann M, Velilla E, Pujol A, et al. (September 2010). "Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes". Human Reproduction. 25 (9): 2316–2327. doi:10.1093/humrep/deq180. PMID 20634189.
1 2 3 Biswas U, Wetzker C, Lange J, Christodoulou EG, Seifert M, Beyer A, Jessberger R (Dec 26, 2013). "Meiotic cohesin SMC1β provides prophase I centromeric cohesion and is required for multiple synapsis-associated functions". PLOS Genetics. 9 (12): e1003985. doi: 10.1371/journal.pgen.1003985 . PMC 3873225 . PMID 24385917.
↑ Eijpe M, Offenberg H, Jessberger R, Revenkova E, Heyting C (March 2003). "Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1beta and SMC3". The Journal of Cell Biology. 160 (5): 657–670. doi:10.1083/jcb.200212080. PMC 2173354 . PMID 12615909.
↑ Novak I, Wang H, Revenkova E, Jessberger R, Scherthan H, Höög C (January 2008). "Cohesin Smc1beta determines meiotic chromatin axis loop organization". The Journal of Cell Biology. 180 (1): 83–90. doi:10.1083/jcb.200706136. PMC 2213612 . PMID 18180366.
↑ Biswas U, Stevense M, Jessberger R (January 2018). "SMC1α Substitutes for Many Meiotic Functions of SMC1β but Cannot Protect Telomeres from Damage". Current Biology. 28 (2): 249–261.e4. doi:10.1016/j.cub.2017.12.020. PMC 5788747 . PMID 29337080.
1 2 Mannini L, Cucco F, Quarantotti V, Amato C, Tinti M, Tana L, et al. (December 2015). "SMC1B is present in mammalian somatic cells and interacts with mitotic cohesin proteins". Scientific Reports. 5: 18472. Bibcode:2015NatSR...518472M. doi:10.1038/srep18472. PMC 4682075 . PMID 26673124.
1 2 3 4 Yi F, Wang Z, Liu J, Zhang Y, Wang Z, Xu H, et al. (Sep 3, 2017). "Structural Maintenance of Chromosomes protein 1: Role in Genome Stability and Tumorigenesis". International Journal of Biological Sciences. 13 (8): 1092–1099. doi:10.7150/ijbs.21206. PMC 5599913 . PMID 28924389.
↑ Milner, Danny (2015). Diagnostic pathology. Infectious diseases. Danny A., Jr. Milner, Nicole Pecora, Isaac Solomon, Thing Rinda Soong. Elsevier Health Sciences. pp. 40–42. ISBN 978-0-323-40037-4. OCLC 921986998.
1 2 Mehta K, Gunasekharan V, Satsuka A, Laimins LA (April 2015). "Human papillomaviruses activate and recruit SMC1 cohesin proteins for the differentiation-dependent life cycle through association with CTCF insulators". PLOS Pathogens. 11 (4): e1004763. doi: 10.1371/journal.ppat.1004763 . PMC 4395367 . PMID 25875106.
↑ Degli Esposti D, Sklias A, Lima SC, Beghelli-de la Forest Divonne S, Cahais V, Fernandez-Jimenez N, et al. (April 2017). "Unique DNA methylation signature in HPV-positive head and neck squamous cell carcinomas". Genome Medicine. 9 (1): 33. doi: 10.1186/s13073-017-0419-z . PMC 5382363 . PMID 28381277.
↑ Boukaba A, Liu J, Ward C, Wu Q, Arnaoutov A, Liang J, et al. (October 2022). "Ectopic expression of meiotic cohesin generates chromosome instability in cancer cell line". Proceedings of the National Academy of Sciences of the United States of America. 119 (40): e2204071119. Bibcode:2022PNAS..11904071B. doi: 10.1073/pnas.2204071119 . PMC 9549395 . PMID 36179046.