1uel

Structural highlights

Function

RD23B_HUMAN Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome. May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins by association with PNGase and delivering deglycosylated proteins to the proteasome.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]} Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with CETN2 appears to stabilize XPC. May protect XPC from proteasomal degradation.^{[12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22]} The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.^{[23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Proteasome 3D structures
• UV excision repair protein

References

1. ↑ Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Mol Cell Biol. 1997 Dec;17(12):6924-31. PMID:9372924
2. ↑ Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998 Aug;2(2):223-32. PMID:9734359
3. ↑ Batty D, Rapic'-Otrin V, Levine AS, Wood RD. Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. J Mol Biol. 2000 Jul 7;300(2):275-90. PMID:10873465 doi:10.1006/jmbi.2000.3857
4. ↑ Sugasawa K, Shimizu Y, Iwai S, Hanaoka F. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2002 Jan 22;1(1):95-107. PMID:12509299
5. ↑ Janicijevic A, Sugasawa K, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst). 2003 Mar 1;2(3):325-36. PMID:12547395
6. ↑ Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003 Jul 1;17(13):1630-45. Epub 2003 Jun 18. PMID:12815074 doi:http://dx.doi.org/10.1101/gad.260003
7. ↑ Li X, Demartino GN. Variably modulated gating of the 26S proteasome by ATP and polyubiquitin. Biochem J. 2009 Jul 15;421(3):397-404. doi: 10.1042/BJ20090528. PMID:19435460 doi:http://dx.doi.org/10.1042/BJ20090528
8. ↑ Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F. Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning. Mol Cell. 2009 Nov 25;36(4):642-53. doi: 10.1016/j.molcel.2009.09.035. PMID:19941824 doi:10.1016/j.molcel.2009.09.035
9. ↑ Neher TM, Rechkunova NI, Lavrik OI, Turchi JJ. Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals contacts with both strands of the DNA duplex and spans the DNA adduct. Biochemistry. 2010 Feb 2;49(4):669-78. doi: 10.1021/bi901575h. PMID:20028083 doi:10.1021/bi901575h
10. ↑ Shimizu Y, Uchimura Y, Dohmae N, Saitoh H, Hanaoka F, Sugasawa K. Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions. J Nucleic Acids. 2010 Jul 25;2010. pii: 805698. doi: 10.4061/2010/805698. PMID:20798892 doi:10.4061/2010/805698
11. ↑ Kim B, Ryu KS, Kim HJ, Cho SJ, Choi BS. Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B. FEBS J. 2005 May;272(10):2467-76. PMID:15885096 doi:10.1111/j.1742-4658.2005.04667.x
12. ↑ Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Mol Cell Biol. 1997 Dec;17(12):6924-31. PMID:9372924
13. ↑ Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998 Aug;2(2):223-32. PMID:9734359
14. ↑ Batty D, Rapic'-Otrin V, Levine AS, Wood RD. Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. J Mol Biol. 2000 Jul 7;300(2):275-90. PMID:10873465 doi:10.1006/jmbi.2000.3857
15. ↑ Sugasawa K, Shimizu Y, Iwai S, Hanaoka F. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2002 Jan 22;1(1):95-107. PMID:12509299
16. ↑ Janicijevic A, Sugasawa K, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst). 2003 Mar 1;2(3):325-36. PMID:12547395
17. ↑ Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003 Jul 1;17(13):1630-45. Epub 2003 Jun 18. PMID:12815074 doi:http://dx.doi.org/10.1101/gad.260003
18. ↑ Li X, Demartino GN. Variably modulated gating of the 26S proteasome by ATP and polyubiquitin. Biochem J. 2009 Jul 15;421(3):397-404. doi: 10.1042/BJ20090528. PMID:19435460 doi:http://dx.doi.org/10.1042/BJ20090528
19. ↑ Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F. Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning. Mol Cell. 2009 Nov 25;36(4):642-53. doi: 10.1016/j.molcel.2009.09.035. PMID:19941824 doi:10.1016/j.molcel.2009.09.035
20. ↑ Neher TM, Rechkunova NI, Lavrik OI, Turchi JJ. Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals contacts with both strands of the DNA duplex and spans the DNA adduct. Biochemistry. 2010 Feb 2;49(4):669-78. doi: 10.1021/bi901575h. PMID:20028083 doi:10.1021/bi901575h
21. ↑ Shimizu Y, Uchimura Y, Dohmae N, Saitoh H, Hanaoka F, Sugasawa K. Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions. J Nucleic Acids. 2010 Jul 25;2010. pii: 805698. doi: 10.4061/2010/805698. PMID:20798892 doi:10.4061/2010/805698
22. ↑ Kim B, Ryu KS, Kim HJ, Cho SJ, Choi BS. Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B. FEBS J. 2005 May;272(10):2467-76. PMID:15885096 doi:10.1111/j.1742-4658.2005.04667.x
23. ↑ Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Mol Cell Biol. 1997 Dec;17(12):6924-31. PMID:9372924
24. ↑ Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998 Aug;2(2):223-32. PMID:9734359
25. ↑ Batty D, Rapic'-Otrin V, Levine AS, Wood RD. Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. J Mol Biol. 2000 Jul 7;300(2):275-90. PMID:10873465 doi:10.1006/jmbi.2000.3857
26. ↑ Sugasawa K, Shimizu Y, Iwai S, Hanaoka F. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2002 Jan 22;1(1):95-107. PMID:12509299
27. ↑ Janicijevic A, Sugasawa K, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst). 2003 Mar 1;2(3):325-36. PMID:12547395
28. ↑ Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003 Jul 1;17(13):1630-45. Epub 2003 Jun 18. PMID:12815074 doi:http://dx.doi.org/10.1101/gad.260003
29. ↑ Li X, Demartino GN. Variably modulated gating of the 26S proteasome by ATP and polyubiquitin. Biochem J. 2009 Jul 15;421(3):397-404. doi: 10.1042/BJ20090528. PMID:19435460 doi:http://dx.doi.org/10.1042/BJ20090528
30. ↑ Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F. Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning. Mol Cell. 2009 Nov 25;36(4):642-53. doi: 10.1016/j.molcel.2009.09.035. PMID:19941824 doi:10.1016/j.molcel.2009.09.035
31. ↑ Neher TM, Rechkunova NI, Lavrik OI, Turchi JJ. Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals contacts with both strands of the DNA duplex and spans the DNA adduct. Biochemistry. 2010 Feb 2;49(4):669-78. doi: 10.1021/bi901575h. PMID:20028083 doi:10.1021/bi901575h
32. ↑ Shimizu Y, Uchimura Y, Dohmae N, Saitoh H, Hanaoka F, Sugasawa K. Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions. J Nucleic Acids. 2010 Jul 25;2010. pii: 805698. doi: 10.4061/2010/805698. PMID:20798892 doi:10.4061/2010/805698
33. ↑ Kim B, Ryu KS, Kim HJ, Cho SJ, Choi BS. Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B. FEBS J. 2005 May;272(10):2467-76. PMID:15885096 doi:10.1111/j.1742-4658.2005.04667.x
34. ↑ Fujiwara K, Tenno T, Sugasawa K, Jee JG, Ohki I, Kojima C, Tochio H, Hiroaki H, Hanaoka F, Shirakawa M. Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B. J Biol Chem. 2004 Feb 6;279(6):4760-7. Epub 2003 Oct 29. PMID:14585839 doi:10.1074/jbc.M309448200