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Updated: May 12, 2026

Electrophoretic Analysis of Replication Through Structure-Prone DNA Repeats Within the SV40-Based Human Episome
05:22

Electrophoretic Analysis of Replication Through Structure-Prone DNA Repeats Within the SV40-Based Human Episome

Published on: September 13, 2024

ATM and ATR activities maintain replication fork integrity during SV40 chromatin replication

Gregory A Sowd1, Nancy Yan Li, Ellen Fanning

  • 1Department of Biological Sciences, Vanderbilt University, Vanderbilt Ingram Comprehensive Cancer Center, Nashville, Tennessee, United States of America.

Plos Pathogens
|April 18, 2013
PubMed

Insights

DNA damage kinases ataxia telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) are crucial for genomic stability. This study reveals ATM repairs replication-associated breaks, while ATR prevents fork breakage during DNA replication.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • Mutations in DNA damage checkpoint kinases ataxia telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) lead to genomic instability.
  • The precise relationship between genomic instability, DNA replication/repair defects, and failed cell cycle checkpoint control in these syndromes remains unclear.

Purpose of the Study:

  • To investigate the roles of ATM and ATR in maintaining genome stability during DNA replication.
  • To elucidate how ATM and ATR signaling pathways respond to replication stress in a model system.

Main Methods:

  • Utilized SV40 chromatin replication as a model system in infected cells.
  • Employed inhibitors to block ATM and ATR activities.
  • Analyzed replication products using two-dimensional gel electrophoresis and southern blotting.

Main Results:

  • ATM activity was found to prevent the accumulation of unidirectional replication products, suggesting a role in repairing replication-associated double-strand breaks.
  • ATR activity was shown to alleviate breakage at converging replication forks.
  • Endogenous replication stress during SV40 chromatin replication activates ATM and ATR signaling.

Conclusions:

  • ATM and ATR play distinct but essential roles in maintaining genome integrity during DNA replication.
  • These kinases orchestrate the recruitment of genome maintenance machinery to viral replication intermediates in response to replication stress.

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