Viral Deregulation of DNA Damage Responses
Sergei Boichuk and Ole Gjoerup
from: Small DNA Tumour Viruses (Edited by: Kevin Gaston). Caister Academic Press, U.K. (2012)
Incoming viral genomes, aberrant viral replication structures or individual viral proteins are potential triggers of DNA damage responses (DDRs). In an emerging theme, viruses interfere with, and frequently commandeer, DDR and repair signaling pathways to promote the viral life cycle. Here we review the diverse mechanisms that small DNA tumour viruses utilize to deregulate DDR pathways. Adenoviruses (Ad) encode gene products that specifically degrade the MRN (Mre11, Rad50, Nbs1) damage sensor or sequester it in nuclear tracks. This causes an inhibition of both ATM and ATR responses. Failure to inactivate MRN leads to attenuation of viral replication and concatemerization of the viral genome, thus preventing efficient packaging. Conversely, polyomaviruses, like SV40, as well as human papillomaviruses (HPVs) appear to exploit the DDR, since they use components of it to positively regulate their life cycle, while generally inhibiting downstream checkpoint responses. SV40, mouse polyomavirus and HPV activate ATM signaling and benefit from it. Complexities of the interplay between small DNA tumour viruses and the DDR are continuously evolving and illuminate both critical aspects of the viral life cycle as well as basic cellular mechanisms operating in a non-viral setting read more ...