ChlR1 Is Required for Loading Papillomavirus E2 onto Mitotic Chromosomes and Viral Genome Maintenance

Joanna L. Parish; Angela M. Bean; Regina B. Park; Elliot J. Androphy

doi:10.1016/j.molcel.2006.11.005

ChlR1 Is Required for Loading Papillomavirus E2 onto Mitotic Chromosomes and Viral Genome Maintenance

Joanna L. Parish, Angela M. Bean, Regina B. Park, Elliot J. Androphy^*

^*Corresponding author for this work

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Autonomously replicating DNA viruses must evade mitotic checkpoints and actively partition their genomes to maintain persistent infection. The E2 protein serves these functions by tethering papillomavirus episomes to mitotic chromosomes; however, the mechanism remains unresolved. We show that E2 binds ChlR1, a DNA helicase that plays a role in sister chromatid cohesion. The E2 mutation W130R fails to bind ChlR1 and correspondingly does not associate with mitotic chromosomes. Viral genomes encoding this E2 mutation are not episomally maintained in cell culture. Notably, E2 W130R binds Brd4, which reportedly acts as a mitotic tether, indicating this interaction is insufficient for E2 association with mitotic chromosomes. RNAi-induced depletion of ChlR1 significantly reduced E2 localization to mitotic chromosomes. These studies provide compelling evidence that ChlR1 association is required for loading the papillomavirus E2 protein onto mitotic chromosomes and represents a kinetochore-independent mechanism for viral genome maintenance and segregation.

Original language	English
Pages (from-to)	867-876
Number of pages	10
Journal	Molecular Cell
Volume	24
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2006.11.005
Publication status	Published - 28 Dec 2006

Bibliographical note

Funding Information:
We thank S. Doxsey and J. Rosa (University of Massachusetts) and J. Lahti (St Jude Children's Research Hospital) for useful discussions. A. McBride and J. Oliveira (NIAIH) provided CV-1-derived pMEP-E2b, -16E2, and -11E2 cell lines. P. James (University of Wisconsin) provided genomic libraries and strains used for the yeast two-hybrid screen. This work was supported by the NIH R01 CA58376 to E. Androphy.

Keywords

DNA
MICROBIO

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2006.11.005

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title = "ChlR1 Is Required for Loading Papillomavirus E2 onto Mitotic Chromosomes and Viral Genome Maintenance",

abstract = "Autonomously replicating DNA viruses must evade mitotic checkpoints and actively partition their genomes to maintain persistent infection. The E2 protein serves these functions by tethering papillomavirus episomes to mitotic chromosomes; however, the mechanism remains unresolved. We show that E2 binds ChlR1, a DNA helicase that plays a role in sister chromatid cohesion. The E2 mutation W130R fails to bind ChlR1 and correspondingly does not associate with mitotic chromosomes. Viral genomes encoding this E2 mutation are not episomally maintained in cell culture. Notably, E2 W130R binds Brd4, which reportedly acts as a mitotic tether, indicating this interaction is insufficient for E2 association with mitotic chromosomes. RNAi-induced depletion of ChlR1 significantly reduced E2 localization to mitotic chromosomes. These studies provide compelling evidence that ChlR1 association is required for loading the papillomavirus E2 protein onto mitotic chromosomes and represents a kinetochore-independent mechanism for viral genome maintenance and segregation.",

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note = "Funding Information: We thank S. Doxsey and J. Rosa (University of Massachusetts) and J. Lahti (St Jude Children's Research Hospital) for useful discussions. A. McBride and J. Oliveira (NIAIH) provided CV-1-derived pMEP-E2b, -16E2, and -11E2 cell lines. P. James (University of Wisconsin) provided genomic libraries and strains used for the yeast two-hybrid screen. This work was supported by the NIH R01 CA58376 to E. Androphy. ",

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AU - Parish, Joanna L.

AU - Bean, Angela M.

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AU - Androphy, Elliot J.

N1 - Funding Information: We thank S. Doxsey and J. Rosa (University of Massachusetts) and J. Lahti (St Jude Children's Research Hospital) for useful discussions. A. McBride and J. Oliveira (NIAIH) provided CV-1-derived pMEP-E2b, -16E2, and -11E2 cell lines. P. James (University of Wisconsin) provided genomic libraries and strains used for the yeast two-hybrid screen. This work was supported by the NIH R01 CA58376 to E. Androphy.

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N2 - Autonomously replicating DNA viruses must evade mitotic checkpoints and actively partition their genomes to maintain persistent infection. The E2 protein serves these functions by tethering papillomavirus episomes to mitotic chromosomes; however, the mechanism remains unresolved. We show that E2 binds ChlR1, a DNA helicase that plays a role in sister chromatid cohesion. The E2 mutation W130R fails to bind ChlR1 and correspondingly does not associate with mitotic chromosomes. Viral genomes encoding this E2 mutation are not episomally maintained in cell culture. Notably, E2 W130R binds Brd4, which reportedly acts as a mitotic tether, indicating this interaction is insufficient for E2 association with mitotic chromosomes. RNAi-induced depletion of ChlR1 significantly reduced E2 localization to mitotic chromosomes. These studies provide compelling evidence that ChlR1 association is required for loading the papillomavirus E2 protein onto mitotic chromosomes and represents a kinetochore-independent mechanism for viral genome maintenance and segregation.

AB - Autonomously replicating DNA viruses must evade mitotic checkpoints and actively partition their genomes to maintain persistent infection. The E2 protein serves these functions by tethering papillomavirus episomes to mitotic chromosomes; however, the mechanism remains unresolved. We show that E2 binds ChlR1, a DNA helicase that plays a role in sister chromatid cohesion. The E2 mutation W130R fails to bind ChlR1 and correspondingly does not associate with mitotic chromosomes. Viral genomes encoding this E2 mutation are not episomally maintained in cell culture. Notably, E2 W130R binds Brd4, which reportedly acts as a mitotic tether, indicating this interaction is insufficient for E2 association with mitotic chromosomes. RNAi-induced depletion of ChlR1 significantly reduced E2 localization to mitotic chromosomes. These studies provide compelling evidence that ChlR1 association is required for loading the papillomavirus E2 protein onto mitotic chromosomes and represents a kinetochore-independent mechanism for viral genome maintenance and segregation.

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ChlR1 Is Required for Loading Papillomavirus E2 onto Mitotic Chromosomes and Viral Genome Maintenance

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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