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Adenovirus E1A oncogene induces rereplication of cellular DNA and alters DNA replication dynamics

Ghata Singhal1, Elisabetta Leo, Saayi Krushna Gadham Setty

  • 1Microbiology and Immunology Department, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

Journal of Virology
|June 7, 2013
PubMed

Insights

Adenovirus E1A protein causes massive DNA rereplication in quiescent cells, altering replication dynamics and inducing replication stress. E1A-induced c-Myc may contribute to these oncogenic events.

Area of Science:

  • Molecular Biology
  • Oncology
  • Virology

Background:

  • The adenovirus (Ad) E1A oncoprotein drives cellular DNA synthesis by interacting with host proteins like pRb and p300/CBP.
  • The precise nature of E1A-induced DNA replication in quiescent cells remains unclear.

Purpose of the Study:

  • To investigate the characteristics of cellular DNA replication induced by E1A in quiescent cells.
  • To elucidate the role of c-Myc in E1A-mediated DNA replication.

Main Methods:

  • Single-molecule DNA fiber assays were employed to analyze DNA replication dynamics.
  • Antisense c-Myc was used to inhibit c-Myc expression and assess its contribution.

Main Results:

  • E1A expression induced massive DNA rereplication in late S phase.
  • Replication patterns showed increased replicon length, fork velocity, and a 3-fold increase in interorigin distance, indicating fewer origins used.
  • Aberrant replication triggered a DNA damage response, and c-Myc induction was found to contribute to host DNA replication.

Conclusions:

  • E1A oncogene induces cellular DNA replication stress through significantly altered replication events.
  • E1A-induced c-Myc plays a role in these oncogenic replication alterations.

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