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DNA-PK phosphorylation at Ser2056 during adenovirus E4 mutant infection is promoted by viral DNA replication and independent of the MRN complex.

Authors :
Chen, Christopher
Bridge, Eileen
Source :
Virology. Jan2022, Vol. 565, p82-95. 14p.
Publication Year :
2022

Abstract

Adenovirus (Ad) early region 4 (E4) mutants activate cellular DNA damage responses (DDRs) that include non-homologous end joining (NHEJ) pathways mediated by the DNA repair kinase DNA-PK and its associated factors Ku70/Ku86. NHEJ results in concatenation of the viral linear double-stranded DNA genome and inhibits a productive infection. E4 proteins normally prevent activation of cellular DDRs in wild-type Ad type 5 (Ad5) infections, thereby promoting efficient viral growth. The purpose of this study was to evaluate the factors that govern DNA-PK activation during adenovirus infection. Our data indicate that viral DNA replication promotes DNA-PK activation, which is required for genome concatenation by NHEJ. Although the Mre11/Rad50/Nbs1 (MRN) DDR sensor complex is not required for DNA-PK activation, Mre11 is important for recruitment of the NHEJ factor Ku86 to viral replication centers. Our study addresses the interplay between the DNA-PK and MRN complexes during viral genome concatenation by NHEJ. • Viral DNA replication promotes DNA-PK activation and genome concatenation during E4-infection. • The MRN complex is not essential for DNA-PK autophosphorylation at Ser2056. • Ku86 is transiently localized to viral replication centers, which is promoted by the MRN complex. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00426822
Volume :
565
Database :
Academic Search Index
Journal :
Virology
Publication Type :
Academic Journal
Accession number :
153751331
Full Text :
https://doi.org/10.1016/j.virol.2021.10.011