Alternative titles; symbols
HGNC Approved Gene Symbol: REC8
Cytogenetic location: 14q12 Genomic coordinates (GRCh38) : 14:24,172,080-24,180,923 (from NCBI)
REC8 is the human homolog of yeast Rec8, a meiosis-specific phosphoprotein involved in recombination events (Parisi et al., 1999).
By searching an EST database for sequences similar to HR21 (RAD21 606462), followed by screening a T-cell leukemia cDNA library, Parisi et al. (1999) cloned REC8. The deduced 547-amino acid protein has a high proline content, a nuclear localization signal, and a putative PEST sequence. REC8 shares about 26% amino acid identity with RAD21. Northern blot analysis detected a 2.4-kb transcript in postmeiotic mouse testis and transcripts of about 2.4 and 3.2 kb in human thymus.
By FISH, Parisi et al. (1999) mapped the REC8 gene to chromosome 14q11.2-q12.
Parisi et al. (1999) determined that expression of yeast Rec8 was meiosis specific and that Rec8 localized to approximately 100 foci per prophase nucleus. Rec8 was present in an unphosphorylated form early in meiotic prophase but was phosphorylated prior to meiosis I.
Brar et al. (2006) showed that phosphorylation of the cohesin subunit REC8 contributes to stepwise cohesin removal. Their data further implicated 2 other key regulators of meiotic chromosome segregation, the cohesin protector SGO1 (SGOL1; 609168) and meiotic recombination in bringing about the stepwise loss of cohesins and thus the establishment of the meiotic chromosome segregation pattern.
Associations Pending Confirmation
By whole-exome sequencing in a cohort of 80 women diagnosed with premature ovarian insufficiency (see POF1, 311360), Tucker et al. (2022) identified a 19-year-old French woman (patient 6) who was compound heterozygous for mutations in the REC8 gene: a 1-bp duplication (c.1035_1036dup) in exon 13, causing a frameshift predicted to result in a premature termination codon (Glu346GlyfsTer72), and a splice site mutation in intron 7 (c.624+1G-A), predicted to disrupt gene splicing. Her unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in the gnomAD database. The proband underwent menarche at age 14 years, developed oligomenorrhea after 1.5 years, and experienced amenorrhea at age 16. Evaluation at age 19 showed elevated follicle-stimulating hormone (FSH; see 136530) and low estradiol and anti-mullerian hormone (AMH; 600957) levels; pelvic ultrasound was not performed. The authors noted that her 49-year-old heterozygous mother had not reached menopause, suggesting that haploinsufficiency of REC8 is tolerated.
Xu et al. (2005) found that Rec8-null mice were born in submendelian frequencies and failed to thrive. Mutant mice of both sexes had germ cell failure and were sterile. In the absence of Rec8, meiocytes failed to complete meiotic prophase I, and synaptonemal complexes formed between sister chromatids rather than between homologous chromosomes. Xu et al. (2005) concluded that REC8 is required for the proper formation of synaptonemal complexes during meiosis.
Brar, G. A., Kiburz, B. M., Zhang, Y., Kim, J.-E., White, F., Amon, A. Rec8 phosphorylation and recombination promote the step-wise loss of cohesins in meiosis. Nature 441: 532-536, 2006. [PubMed: 16672979] [Full Text: https://doi.org/10.1038/nature04794]
Parisi, S., McKay, M. J., Molnar, M., Thompson, M. A., van der Spek, P. J., van Drunen-Schoenmaker, E., Kanaar, R., Lehmann, E., Hoeijmakers, J. H. J., Kohli, J. Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of the Rad21p family conserved from fission yeast to humans. Molec. Cell. Biol. 19: 3515-3528, 1999. [PubMed: 10207075] [Full Text: https://doi.org/10.1128/MCB.19.5.3515]
Tucker, E. J., Bell, K. M., Robevska, G., van den Bergen, J., Ayers, K. L., Listyasari, N., Faradz, S. M. H., Dulon, J., Bakhshalizadeh, S., Sreenivasan, R., Nouyou, B., Carre, W., Akloul, L., Duros, S., Domin-Bernhard, M., Belaud-Rotureau, M.-A., Touraine, P., Jaillard, S., Sinclair, A. H. Meiotic genes in premature ovarian insufficiency: variants in HROB and REC8 as likely genetic causes. Europ. J. Hum. Genet. 30: 219-228, 2022. [PubMed: 34707299] [Full Text: https://doi.org/10.1038/s41431-021-00977-9]
Xu, H., Beasley, M. D., Warren, W. D., van der Horst, G. T. J., McKay, M. J. Absence of mouse REC8 cohesin promotes synapsis of sister chromatids in meiosis. Dev. Cell 8: 949-961, 2005. [PubMed: 15935783] [Full Text: https://doi.org/10.1016/j.devcel.2005.03.018]