Localization of the Kinase Ataxia Telangiectasia Mutated to Adenovirus E4 Mutant DNA Replication Centers is Important for Its Inhibitory Effect on Viral DNA Accumulation

Overview

Journal Virology

Specialty Microbiology

Date 2018 Nov 20

PMID 30453211

Citations 1

Authors

Dipendra Gautam

Gabrielle Stanley

Mary Owen

Eileen Bridge

Affiliations

Soon will be listed here.

Abstract

Adenovirus (Ad) type 5 (Ad5) E4 deletion mutants including H5dl1007 (E4-) induce a DNA damage response (DDR) that activates the kinase ataxia-telangiectasia mutated (ATM), which can interfere with efficient viral DNA replication. We find that localization of active phosphorylated ATM (pATM) to E4- viral replication centers (VRCs) is important for its inhibitory effect. ATM is necessary for localization of RNF8 and 53BP1 to E4 mutant VRCs, while recruitment of DDR factors Mre11, Mdc1 and γH2AX is ATM-independent, raising the possibility that ATM may affect viral chromatin at VRCs. We assessed E4- and Ad5 chromatin organization by micrococcal nuclease (MN) digestion. A significant fraction of Ad5 DNA is somewhat resistant to MN digestion, whereas E4- DNA is more susceptible. ATM inhibition increases the fraction of E4- DNA that is resistant to MN digestion. Our results address possible mechanisms through which ATM inhibits E4- DNA replication.

Citing Articles

En Guard! The Interactions between Adenoviruses and the DNA Damage Response.

Kleinberger T Viruses. 2020; 12(9).

PMID: 32906746 PMC: 7552057. DOI: 10.3390/v12090996.

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