Alternative titles; symbols
HGNC Approved Gene Symbol: SMC1B
Cytogenetic location: 22q13.31 Genomic coordinates (GRCh38) : 22:45,344,063-45,413,599 (from NCBI)
SMC1L2 belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis (3:Revenkova et al., 2001).
Revenkova et al. (2001) cloned mouse Smc1l2, which they designated Smc1-beta, from a testis cDNA library. The deduced 1,248-amino acid protein has an N-terminal Walker A box, a central ABC ATPase (see 601691) signature motif, and a C-terminal Walker B box. It also has an extended coiled-coil domain with heptad repeats and a hinge region. Smc1l2 shares highest similarity with Smc1 (300040). Northern blot analysis of several mouse tissues detected a 4.5-kb Smc1l2 transcript only in testis. In rat spermatocytes, Smc1l2 localized along the axial elements (AEs) of synaptonemal complexes in prophase I. Most Smc1l2 dissociated from the chromosome arms in late-pachytene-diplotene cells. Smc1l2 remained associated with chromatin at the centromeres up to metaphase II. Smc1l2 purified from mouse or bovine testis nuclear extracts had an apparent molecular mass of about 150 kD by SDS-PAGE.
Using a filter binding assay, Revenkova et al. (2001) determined that a 28-amino acid motif in the C terminus of mouse Smc1l2 bound DNA. Smc1l2 coprecipitated with Smc3 (606062) from bovine testis nuclear extracts.
Hartz (2004) mapped the SMC1L2 gene to chromosome 22q13.31 based on an alignment of the SMC1L2 sequence (GenBank AJ504806) with the genomic sequence.
Revenkova et al. (2004) found that both male and female mice deficient in Smc1l2 were sterile. Male meiosis was blocked at the pachytene stage, and female meiosis was highly error prone but continued until metaphase II. Prophase AEs were markedly shortened, chromatin extended further from the AEs, chromosome synapsis was incomplete, and sister chromatid cohesion in chromosome arms and at centromeres was lost prematurely. In addition, crossover-associated recombination foci were absent or reduced, and meiosis-specific perinuclear telomere arrangements were impaired. Revenkova et al. (2004) concluded that SMC1L2 has a key role in meiotic cohesion, the assembly of AEs, synapsis, recombination, and chromosome movements.
Meiotic cell division requires that cohesion be released sequentially to facilitate orderly segregation of chromosomes at both meiosis I and meiosis II. This necessitates meiosis-specific cohesin components; studies in rodents have suggested that these influence chromosome behavior during both cell division and meiotic prophase. To elucidate the role of the meiosis-specific cohesin SMC1-beta, encoded by Smc1l2, in oogenesis, Hodges et al. (2005) carried out meiotic studies of female SMC1-beta-deficient mice. Their results provided the first direct evidence that SMC1-beta acts as a chiasma binder in mammals, stabilizing sites of exchange until anaphase. Additionally, the observations supported the hypothesis that deficient cohesion is an underlying cause of human age-related aneuploidy.
Hartz, P. A. Personal Communication. Baltimore, Md. 5/25/2004.
Hodges, C. A., Revenkova, E., Jessberger, R., Hassold, T. J., Hunt, P. A. SMC1-beta-deficient female mice provide evidence that cohesins are a missing link in age-related nondisjunction. Nature Genet. 37: 1351-1355, 2005. [PubMed: 16258540] [Full Text: https://doi.org/10.1038/ng1672]
Revenkova, E., Eijpe, M., Heyting, C., Gross, B., Jessberger, R. Novel meiosis-specific isoform of mammalian SMC1. Molec. Cell. Biol. 21: 6984-6998, 2001. [PubMed: 11564881] [Full Text: https://doi.org/10.1128/MCB.21.20.6984-6998.2001]
Revenkova, E., Eijpe, M., Heyting, C., Hodges, C. A., Hunt, P. A., Liebe, B., Scherthan, H., Jessberger, R. Cohesin SMC1-beta is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination. Nature Cell Biol. 6: 555-562, 2004. [PubMed: 15146193] [Full Text: https://doi.org/10.1038/ncb1135]