| Structural highlights
Function
[TOPB1_HUMAN] Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double-stranded DNA breaks and nicks as well as single-stranded DNA. Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage. Induces a large increase in the kinase activity of ATR.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Human DNA Topoisomerase IIbeta binding protein 1 (TopBP1) is a modulating protein that plays an essential role in the response to DNA damage. The N-terminal region of TopBP1, which contains predicted BRCA1-carboxy terminal (BRCT) domains 1 and 2, binds to Rad9, a component of the cell cycle checkpoint clamp Rad9-Hus1-Rad1 complex. Here, we report the crystal structure of the TopBP1N-terminal region (residues 1-290) at 2.4A resolution. Interestingly, in addition to the predicted tandem BRCT1-2 repeats (residues 103-284), residues 7-98 form a previously unreported BRCT domain (here, BRCT0). In contrast to both BRCT1 and BRCT2, which possess the conventional phosphopeptide binding residues within a surface pocket, the corresponding pocket in BRCT0 is largely hydrophobic. Structural comparisons together with peptide binding studies indicate that the tandem BRCT1-2 domains are the binding region for phosphorylated Ser387 in Rad9.
Crystal structure of the N-terminal region of human Topoisomerase IIbeta binding protein 1.,Huo YG, Bai L, Xu M, Jiang T Biochem Biophys Res Commun. 2010 Oct 22;401(3):401-5. Epub 2010 Sep 19. PMID:20858457[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yamane K, Tsuruo T. Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA. Oncogene. 1999 Sep 16;18(37):5194-203. PMID:10498869 doi:10.1038/sj.onc.1202922
- ↑ Makiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Makela TP, Syvaoja JE. BRCT domain-containing protein TopBP1 functions in DNA replication and damage response. J Biol Chem. 2001 Aug 10;276(32):30399-406. Epub 2001 Jun 6. PMID:11395493 doi:10.1074/jbc.M102245200
- ↑ Honda Y, Tojo M, Matsuzaki K, Anan T, Matsumoto M, Ando M, Saya H, Nakao M. Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response. J Biol Chem. 2002 Feb 1;277(5):3599-605. Epub 2001 Nov 19. PMID:11714696 doi:10.1074/jbc.M104347200
- ↑ Liu K, Lin FT, Ruppert JM, Lin WC. Regulation of E2F1 by BRCT domain-containing protein TopBP1. Mol Cell Biol. 2003 May;23(9):3287-304. PMID:12697828
- ↑ Liu K, Luo Y, Lin FT, Lin WC. TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival. Genes Dev. 2004 Mar 15;18(6):673-86. PMID:15075294 doi:10.1101/gad.1180204
- ↑ Kumagai A, Lee J, Yoo HY, Dunphy WG. TopBP1 activates the ATR-ATRIP complex. Cell. 2006 Mar 10;124(5):943-55. PMID:16530042 doi:10.1016/j.cell.2005.12.041
- ↑ Huo YG, Bai L, Xu M, Jiang T. Crystal structure of the N-terminal region of human Topoisomerase IIbeta binding protein 1. Biochem Biophys Res Commun. 2010 Oct 22;401(3):401-5. Epub 2010 Sep 19. PMID:20858457 doi:10.1016/j.bbrc.2010.09.066
|
