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Gene Review

RAD21  -  RAD21 homolog (S. pombe)

Homo sapiens

Synonyms: CDLS4, Double-strand-break repair protein rad21 homolog, HR21, HRAD21, KIAA0078, ...
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Disease relevance of RAD21


High impact information on RAD21

  • Separation of sister chromatids in anaphase is mediated by separase, an endopeptidase that cleaves the chromosomal cohesin SCC1 [4].
  • Mapping of hRAD21, SNF2h and Mi2 binding sites by chromatin immunoprecipitation experiments reveals the specific association of these three proteins with human DNA elements containing Alu sequences [5].
  • Nuclear matrix attachment regions (MARs) are regulatory DNA sequences that are important for higher-order chromatin organization, long-range enhancer function, and extension of chromatin modifications [6].
  • Immunocytochemical analysis revealed abnormalities in the localization of two heterochromatin proteins, Rad21 cohesin protein and BubR1 checkpoint protein, but the localization of core kinetochore proteins such as centromere protein (CENP)-A and -C was normal [7].
  • Azotobacter chroococcum MCD1 contains a cluster of nitrogen fixation (nif) genes coding for the structural polypeptides for nitrogenase (nifH for the Fe-protein and nifD and nifK for the MoFe protein) and a second sequence in the genome homologous to nifH [8].

Chemical compound and disease context of RAD21


Biological context of RAD21

  • RAD21 is a component of the cohesin complex that holds sister chromatids together during mitosis and repairs double-strand DNA breaks [13].
  • Caspase proteolysis of the cohesin component RAD21 promotes apoptosis [13].
  • Interestingly, RAD21 is cleaved by a caspase-like Esp1/separase at the onset of anaphase to trigger sister chromatid separation [13].
  • We also demonstrate that caspase proteolysis of RAD21 precedes apoptotic chromatin condensation and has important functional consequences, viz. the partial removal of RAD21 from chromatin and the production of a proapoptotic carboxyl-terminal cleavage product that amplifies the cell death signal [13].
  • We studied replacement of the mitotic by the meiotic cohesin complex during mouse germinal cell maturation, and we show that mammalian STAG2 and Rad21 are also involved in several meiosis stages [14].

Anatomical context of RAD21


Associations of RAD21 with chemical compounds


Physical interactions of RAD21

  • Nuclear matrix binding regulates SATB1-mediated transcriptional repression [23].
  • Nuclear matrix-bound RB was detectable in all cases, indicating that loss of RB is not responsible for decreased class II expression in these lines [24].

Enzymatic interactions of RAD21

  • Here, we demonstrate that human RAD21 is preferentially cleaved at Asp(279) by caspases-3 and -7 in vitro to generate two major proteolytic products of approximately 65 and 48 kDa [13].

Other interactions of RAD21


Analytical, diagnostic and therapeutic context of RAD21


  1. RAD21 and KIAA0196 at 8q24 are amplified and overexpressed in prostate cancer. Porkka, K.P., Tammela, T.L., Vessella, R.L., Visakorpi, T. Genes Chromosomes Cancer (2004) [Pubmed]
  2. Suppression of RAD21 gene expression decreases cell growth and enhances cytotoxicity of etoposide and bleomycin in human breast cancer cells. Atienza, J.M., Roth, R.B., Rosette, C., Smylie, K.J., Kammerer, S., Rehbock, J., Ekblom, J., Denissenko, M.F. Mol. Cancer Ther. (2005) [Pubmed]
  3. Correlation of invasion and metastasis of cancer cells, and expression of the RAD21 gene in oral squamous cell carcinoma. Yamamoto, G., Irie, T., Aida, T., Nagoshi, Y., Tsuchiya, R., Tachikawa, T. Virchows Arch. (2006) [Pubmed]
  4. Dual inhibition of sister chromatid separation at metaphase. Stemmann, O., Zou, H., Gerber, S.A., Gygi, S.P., Kirschner, M.W. Cell (2001) [Pubmed]
  5. A chromatin remodelling complex that loads cohesin onto human chromosomes. Hakimi, M.A., Bochar, D.A., Schmiesing, J.A., Dong, Y., Barak, O.G., Speicher, D.W., Yokomori, K., Shiekhattar, R. Nature (2002) [Pubmed]
  6. SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression. Dobreva, G., Dambacher, J., Grosschedl, R. Genes Dev. (2003) [Pubmed]
  7. Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Fukagawa, T., Nogami, M., Yoshikawa, M., Ikeno, M., Okazaki, T., Takami, Y., Nakayama, T., Oshimura, M. Nat. Cell Biol. (2004) [Pubmed]
  8. Second gene (nifH*) coding for a nitrogenase iron protein in Azotobacter chroococcum is adjacent to a gene coding for a ferredoxin-like protein. Robson, R., Woodley, P., Jones, R. EMBO J. (1986) [Pubmed]
  9. Nuclear matrix targeting of the protein kinase CK2 signal as a common downstream response to androgen or growth factor stimulation of prostate cancer cells. Guo, C., Yu, S., Davis, A.T., Ahmed, K. Cancer Res. (1999) [Pubmed]
  10. Adenovirus precursor to terminal protein interacts with the nuclear matrix in vivo and in vitro. Fredman, J.N., Engler, J.A. J. Virol. (1993) [Pubmed]
  11. Curcumin suppresses growth of head and neck squamous cell carcinoma. LoTempio, M.M., Veena, M.S., Steele, H.L., Ramamurthy, B., Ramalingam, T.S., Cohen, A.N., Chakrabarti, R., Srivatsan, E.S., Wang, M.B. Clin. Cancer Res. (2005) [Pubmed]
  12. Opioids and differentiation in human cancer cells. Zagon, I.S., McLaughlin, P.J. Neuropeptides (2005) [Pubmed]
  13. Caspase proteolysis of the cohesin component RAD21 promotes apoptosis. Chen, F., Kamradt, M., Mulcahy, M., Byun, Y., Xu, H., McKay, M.J., Cryns, V.L. J. Biol. Chem. (2002) [Pubmed]
  14. STAG2 and Rad21 mammalian mitotic cohesins are implicated in meiosis. Prieto, I., Pezzi, N., Buesa, J.M., Kremer, L., Barthelemy, I., Carreiro, C., Roncal, F., Martinez, A., Gomez, L., Fernandez, R., Martinez-A, C., Barbero, J.L. EMBO Rep. (2002) [Pubmed]
  15. Cohesin component dynamics during meiotic prophase I in mammalian oocytes. Prieto, I., Tease, C., Pezzi, N., Buesa, J.M., Ortega, S., Kremer, L., Martínez, A., Martínez-A, C., Hultén, M.A., Barbero, J.L. Chromosome Res. (2004) [Pubmed]
  16. Nuclear matrix proteins as structural and functional components of the mitotic apparatus. He, D., Zeng, C., Brinkley, B.R. Int. Rev. Cytol. (1995) [Pubmed]
  17. Sequence conservation of the rad21 Schizosaccharomyces pombe DNA double-strand break repair gene in human and mouse. McKay, M.J., Troelstra, C., van der Spek, P., Kanaar, R., Smit, B., Hagemeijer, A., Bootsma, D., Hoeijmakers, J.H. Genomics (1996) [Pubmed]
  18. NXP-1, a human protein related to Rad21/Scc1/Mcd1, is a component of the nuclear matrix. Sadano, H., Sugimoto, H., Sakai, F., Nomura, N., Osumi, T. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  19. Novel DNA sequence variants in the hHR21 DNA repair gene in radiosensitive cancer patients. Severin, D.M., Leong, T., Cassidy, B., Elsaleh, H., Peters, L., Venter, D., Southey, M., McKay, M. Int. J. Radiat. Oncol. Biol. Phys. (2001) [Pubmed]
  20. Nuclear matrix acceptor binding sites for steroid hormone receptors: a candidate nuclear matrix acceptor protein. Lauber, A.H., Sandhu, N.P., Schuchard, M., Subramaniam, M., Spelsberg, T.C. Int. Rev. Cytol. (1995) [Pubmed]
  21. Short-term nitrate (nitrite) inhibition of nitrogen fixation in Azotobacter chroococcum. Cejudo, F.J., Paneque, A. J. Bacteriol. (1986) [Pubmed]
  22. The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model. Ruda, J.M., Beus, K.S., Hollenbeak, C.S., Wilson, R.P., Stack, B.C. Investigational new drugs. (2006) [Pubmed]
  23. Nuclear matrix binding regulates SATB1-mediated transcriptional repression. Seo, J., Lozano, M.M., Dudley, J.P. J. Biol. Chem. (2005) [Pubmed]
  24. RB and a novel E2F-1 binding protein in MHC class II deficient B-cell lines and normal IFN-gamma induction of the class IL transactivator CIITA in class II non-inducible RB-defective tumor lines. Tschickardt, M.E., Lu, Y., Jacim, M., Ussery, G.D., Steimle, V., Mach, B., Blanck, G. Int. J. Cancer (1995) [Pubmed]
  25. A potential role for human cohesin in mitotic spindle aster assembly. Gregson, H.C., Schmiesing, J.A., Kim, J.S., Kobayashi, T., Zhou, S., Yokomori, K. J. Biol. Chem. (2001) [Pubmed]
  26. The DIF1 gene of Arabidopsis is required for meiotic chromosome segregation and belongs to the REC8/RAD21 cohesin gene family. Bhatt, A.M., Lister, C., Page, T., Fransz, P., Findlay, K., Jones, G.H., Dickinson, H.G., Dean, C. Plant J. (1999) [Pubmed]
  27. Hormone-induced chromosomal instability in p53-null mammary epithelium. Pati, D., Haddad, B.R., Haegele, A., Thompson, H., Kittrell, F.S., Shepard, A., Montagna, C., Zhang, N., Ge, G., Otta, S.K., McCarthy, M., Ullrich, R.L., Medina, D. Cancer Res. (2004) [Pubmed]
  28. Nuclear matrix association of the human beta-globin locus utilizing a novel approach to quantitative real-time PCR. Ostermeier, G.C., Liu, Z., Martins, R.P., Bharadwaj, R.R., Ellis, J., Draghici, S., Krawetz, S.A. Nucleic Acids Res. (2003) [Pubmed]
  29. Cohesin is dispensable for centromere cohesion in human cells. Díaz-Martínez, L.A., Giménez-Abián, J.F., Clarke, D.J. PLoS ONE (2007) [Pubmed]
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