The minimum replication origin of merkel cell polyomavirus has a unique large T-antigen loading architecture and requires small T-antigen expression for optimal replication

Journal of Virology
Hyun Jin KwunYuan Chang


Merkel cell polyomavirus (MCV) is a recently discovered human polyomavirus causing the majority of human Merkel cell carcinomas. We mapped a 71-bp minimal MCV replication core origin sufficient for initiating eukaryotic DNA replication in the presence of wild-type MCV large T protein (LT). The origin includes a poly(T)-rich tract and eight variably oriented, GAGGC-like pentanucleotide sequences (PS) that serve as LT recognition sites. Mutation analysis shows that only four of the eight PS are required for origin replication. A single point mutation in one origin PS from a naturally occurring, tumor-derived virus reduces LT assembly on the origin and eliminates viral DNA replication. Tumor-derived LT having mutations truncating either the origin-binding domain or the helicase domain also prevent LT-origin assembly. Optimal MCV replication requires coexpression of MCV small T protein (sT), together with LT. An intact DnaJ domain on the LT is required for replication but is dispensable on the sT. In contrast, PP2A targeting by sT is required for enhanced replication. The MCV origin provides a novel model for eukaryotic replication from a defined DNA element and illustrates the selective pressure within tumors to abrogate independe...Continue Reading


May 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·N BouckG di Mayorca
Jan 1, 1992·Annual Review of Biochemistry·Ellen Fanning, R Knippers
Oct 1, 1992·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R M BenbowD D Larson
Apr 1, 1991·Molecular and Cellular Biology·S I YangM C Mumby
Oct 1, 1987·Molecular and Cellular Biology·C PrivesJ Hurwitz
Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F B DeanJ Hurwitz
Jul 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·K CowanD D Anthony
Aug 1, 1984·Journal of Virology·S J Triezenberg, W R Folk
Oct 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·D C RioR Tjian
Mar 1, 1984·Virology·L S ChangG di Mayorca
Jan 1, 1995·Journal of Virology·M C ChenM M Fluck
Jul 1, 1994·Journal of Virology·S L Spence, J M Pipas
Apr 25, 1997·Journal of Molecular Biology·M C San MartínJ M Carazo
May 1, 1997·Genes & Development·K S CampbellJames A DeCaprio
Mar 9, 2002·Molecular and Cellular Biology·William C HahnRobert A Weinberg
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jul 15, 2005·Journal of Virology·Kerry A WhalenBrian S Schaffhausen
Feb 17, 2006·Journal of Molecular Biology·Mikel ValleJosé María Carazo
Apr 14, 2006·Journal of Virology·Gretchen MeinkeAndrew Bohm
Jan 19, 2008·Science·Huichen FengPatrick S Moore
Sep 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Masahiro ShudaYuan Chang
Dec 17, 2008·The Journal of Investigative Dermatology·Christopher B Buck, Douglas R Lowy
Mar 3, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Eric J DuncavageJohn D Pfeifer
Mar 28, 2009·PLoS Pathogens·Jaime M KeanRobert L Garcea
Apr 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Hanbin LiuArieh Warshel
Apr 28, 2009·Advances in Anatomic Pathology·Melissa P PulitzerKlaus J Busam
May 15, 2009·The British Journal of Dermatology·E VargaL Kemény
Jun 6, 2009·International Journal of Cancer. Journal International Du Cancer·Masahiro ShudaYuan Chang
Jun 6, 2009·International Journal of Cancer. Journal International Du Cancer·Yanis L TolstovPatrick S Moore


Nov 26, 2010·Nature Reviews. Cancer·Patrick S Moore, Yuan Chang
Feb 8, 2013·Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]·Kyle AmberKeyvan Nouri
Aug 16, 2011·The Journal of Clinical Investigation·Masahiro ShudaPatrick S Moore
Jul 30, 2011·PloS One·Huichen FengPatrick S Moore
Apr 4, 2014·PloS One·Christian AdamRoland Houben
Jun 4, 2015·Emerging Microbes & Infections·Masahiko Ajiro, Zhi-Ming Zheng
Sep 29, 2011·Annual Review of Pathology·Yuan Chang, Patrick S Moore
May 27, 2015·Viruses·Robert Hollingworth, Roger J Grand
Oct 25, 2014·Viruses·Abigail Morales-Sánchez, Ezequiel M Fuentes-Pananá
Jun 20, 2012·Current Opinion in Virology·Reety AroraPatrick S Moore
Jun 7, 2011·Human Pathology·Satoshi Kuwamoto
Apr 20, 2011·Journal of Molecular Biology·Celia J HarrisonAndrew Bohm
Feb 24, 2010·Trends in Microbiology·Edward M Johnson
Sep 20, 2015·The Journal of General Virology·Kathleen F RichardsYuan Chang
Nov 13, 2013·The Journal of Investigative Dermatology·Masahiro ShudaPatrick S Moore
Sep 12, 2014·International Journal of Cancer. Journal International Du Cancer·Roland HoubenSonja Hesbacher
Jan 21, 2012·International Journal of Cancer. Journal International Du Cancer·Stephanie K DemetriouDennis H Oh
Dec 12, 2012·Virology·Megan E Spurgeon, Paul F Lambert
Aug 23, 2011·Biochimica Et Biophysica Acta·Julien GuergnonAlphonse Garcia
Feb 15, 2015·Current Opinion in Virology·J A WendzickiYuan Chang
Jun 15, 2010·Cell Host & Microbe·Rachel M SchowalterChristopher B Buck
Jan 29, 2016·Journal of Clinical Pathology·Shakuntala H MauzoPhyu P Aung
Oct 9, 2015·Current Opinion in Virology·Adam Grundhoff, Nicole Fischer
Feb 9, 2017·Canadian Journal of Microbiology·Soumen Bhattacharjee, Sutanuka Chattaraj
Nov 3, 2017·Journal of Virology·Gabrielė StakaitytėAdrian Whitehouse
Dec 15, 2017·Virology : Research and Treatment·Camila Freze BaezSerena Delbue
Jun 23, 2018·Cancers·Maria Lina TorneselloFranco Maria Buonaguro
Jan 30, 2015·Journal of Virology·Hyun Jin KwunPatrick S Moore
Sep 27, 2013·Journal of Virology·Naveed ShahzadMassimo Tommasino
Mar 14, 2019·Future Microbiology·Naveed ShahzadNaeem Rashid
Sep 13, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·James A DeCaprio
Jun 11, 2019·International Journal of Cancer. Journal International Du Cancer·Satendra KumarWeng-Onn Lui
Feb 16, 2020·The Journal of Infectious Diseases·Jennifer Alvarez OrellanaPatrick S Moore
Dec 24, 2011·Médecine sciences : M/S·Angélique N GodetAlphonse Garcia
Jul 1, 2020·Annual Review of Virology·Wei Liu, Jianxin You
May 4, 2017·Proceedings of the National Academy of Sciences of the United States of America·Hyun Jin KwunPatrick S Moore
Oct 6, 2018·Nature Reviews. Clinical Oncology·Paul W HarmsInternational Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group
Apr 27, 2018·Frontiers in Microbiology·Celestino VelásquezMasahiro Shuda
Sep 30, 2020·Viruses·June F Yang, Jianxin You
Jul 9, 2020·Cancers·Valeria PietropaoloUgo Moens
Aug 6, 2020·Molecular Cancer Research : MCR·Jiawei ZhaoRichard C Wang
Apr 20, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ioannis GavvovidisThomas Blankenstein

Related Concepts

Antigens, Neoplasm, Viral
DNA, Viral
Murine polyomavirus
Plasma Protein Binding Capacity
Virus Replication
Point Mutation
Replication Origin
Merkel Cells
Merkel Cell Carcinoma

Related Feeds

BK Virus Infection

BK virus infection is a significant complication of modern immunosuppression used in kidney transplantation. Discover the latest research on BK virus infection here.