Structural highlights
Function
[SGS1_YEAST] Interacts with topoisomerases II and TOP3. Could create a deleterious topological substrate that TOP3 preferentially resolves. The TOP3-SGS1 protein complex may function as a eukaryotic reverse gyrase introducing positive supercoils into extrachromosomal ribosomal DNA rings. Together with topoisomerase II has a role in chromosomal segregation. Maintains rDNA structure where it has a role in re-starting stalled replication forks.[1] [2] [3]
Publication Abstract from PubMed
BACKGROUND: The HRDC (helicase and RNaseD C-terminal) domain is found at the C terminus of many RecQ helicases, including the human Werner and Bloom syndrome proteins. RecQ helicases have been shown to unwind DNA in an ATP-dependent manner. However, the specific functional roles of these proteins in DNA recombination and replication are not known. An HRDC domain exists in both of the human RecQ homologues that are implicated in human disease and may have an important role in their function. RESULTS: We have determined the three-dimensional structure of the HRDC domain in the Saccharomyces cerevisiae RecQ helicase Sgs1p by nuclear magnetic resonance (NMR) spectroscopy. The structure resembles auxiliary domains in bacterial DNA helicases and other proteins that interact with nucleic acids. We show that a positively charged region on the surface of the Sgs1p HRDC domain can interact with DNA. Structural similarities to bacterial DNA helicases suggest that the HRDC domain functions as an auxiliary domain in RecQ helicases. Homology models of the Werner and Bloom HRDC domains show different surface properties when compared with Sgs1p. CONCLUSIONS: The HRDC domain represents a structural scaffold that resembles auxiliary domains in proteins that are involved in nucleic acid metabolism. In Sgs1p, the HRDC domain could modulate the helicase function via auxiliary contacts to DNA. However, in the Werner and Bloom syndrome helicases the HRDC domain may have a role in their functional differences by mediating diverse molecular interactions.
The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins.,Liu Z, Macias MJ, Bottomley MJ, Stier G, Linge JP, Nilges M, Bork P, Sattler M Structure. 1999 Dec 15;7(12):1557-66. PMID:10647186[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gangloff S, McDonald JP, Bendixen C, Arthur L, Rothstein R. The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol Cell Biol. 1994 Dec;14(12):8391-8. PMID:7969174
- ↑ Watt PM, Louis EJ, Borts RH, Hickson ID. Sgs1: a eukaryotic homolog of E. coli RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation. Cell. 1995 Apr 21;81(2):253-60. PMID:7736577
- ↑ Kaliraman V, Brill SJ. Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae. Curr Genet. 2002 Sep;41(6):389-400. Epub 2002 Aug 22. PMID:12228808 doi:http://dx.doi.org/10.1007/s00294-002-0319-6
- ↑ Liu Z, Macias MJ, Bottomley MJ, Stier G, Linge JP, Nilges M, Bork P, Sattler M. The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins. Structure. 1999 Dec 15;7(12):1557-66. PMID:10647186
