The SV40 large T-antigen origin binding domain directly participates in DNA unwinding

Biochemistry
Erin C Foster, Daniel T Simmons

Abstract

The origin binding domain (OBD) of SV40 large T-ag serves a critical role during initiation of DNA replication to position T-ag on the origin. After origin recognition, T-ag forms a double hexamer over the origin. Within each hexamer, the OBD adopts a lock washer structure where the origin recognizing A1 and B2 loops face toward the helicase domain and likely become unavailable for binding DNA. In this study, we investigated the role of the central channel of the OBD hexamer in DNA replication by analyzing the effects of mutations of residues lining the channel. All mutants showed binding defects with origin DNA and ssDNA especially at low protein concentrations, but only half were defective at supporting DNA replication in vitro. All mutants were normal in unwinding linear origin DNA fragments. However, replication defective mutants failed to unwind a small origin containing circular DNA whereas replication competent mutants did so normally. The presence of RPA and/or pol/prim restored circular DNA unwinding activity of compromised mutants probably by interacting with the separated DNA strands on the T-ag surface. We interpret these results to indicate a role for the OBD central channel in binding and threading ssDNA during un...Continue Reading

References

Jan 1, 1992·Annual Review of Biochemistry·E Fanning, R Knippers
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·T MatsumotoJ Hurwitz
Jul 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·C R WobbeJ Hurwitz
Jun 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J M Roberts
Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F B DeanJ Hurwitz
Dec 15, 1987·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·C R WobbeJ Hurwitz
May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·Y MurakamiJ Hurwitz
Aug 1, 1985·Molecular and Cellular Biology·B W Stillman, Y Gluzman
May 1, 1986·Molecular and Cellular Biology·S DebP Tegtmeyer
Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F B DeanJ Hurwitz
Apr 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·C R WobbeJ Hurwitz
Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·J J Li, T J Kelly
Mar 29, 1996·The Journal of Biological Chemistry·L StewartJ J Champoux
Mar 29, 1996·The Journal of Biological Chemistry·L StewartJ J Champoux
Aug 15, 1996·Virology·D T SimmonsB Stillman
Dec 1, 1996·Nature Structural Biology·X LuoW W Bachovchin
Jan 1, 1997·Critical Reviews in Biochemistry and Molecular Biology·P A Bullock
Dec 18, 1998·The Journal of Biological Chemistry·L HalmerC Gruss
Feb 18, 1999·Molecular and Cellular Biology·P W TrowbridgeD T Simmons
Dec 14, 1999·Molecular and Cellular Biology·M ValleL E Donate
Oct 29, 2000·Advances in Virus Research·D T Simmons
Jun 5, 2002·Annual Review of Biochemistry·Ulrich HubscherSilvio Spadari
Feb 13, 2004·Nucleic Acids Research·Daniel T SimmonsRupa Roy
Aug 4, 2004·Genes & Development·Eric A AbbateMichael R Botchan

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Citations

Apr 22, 2008·Molecular Immunology·Kristin Andreassen FentonOle Petter Rekvig
Jan 1, 2012·Genes·Daniel T Simmons

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