Human cytomegalovirus infection modulates DNA base excision repair in fibroblast cells.
Regulation of DNA repair mechanisms during the viral replication cycle may have consequences for the virus with regards to genomic variability, adaptation, and replication of viral DNA. We have studied the activities and expression patterns of key enzymes involved in the first two steps of base excision repair (BER) of DNA in primary fibroblasts infected by human cytomegalovirus (HCMV). Infected cells were very proficient for removal of uracil and 5' hydrolysis of AP sites (AP endonuclease activity) as compared to the mock-infected cells, suggesting a direct role in generating free ends at uracil lesions in DNA for initiation of viral replication. Furthermore, the capacity to initiate repair of alkylated and oxidized base lesions were reduced in HCMV-infected cells, indicating increased mutation frequencies that could promote genetic variability. We hypothesize that modulation of BER activities may play an important role in HCMV pathogenesis to ensure efficient replication and genomic variation of viral DNA.
Ranneberg-Nilsen
Toril
T
Department of Virology, Institute of Microbiology, University of Oslo, Rikshospitalet, Norway. toril.ranneberg-nilsen@medisin.uio.no
Bjørås
Magnar
M
Luna
Luisa
L
Slettebakk
Ragnhild
R
Dale
Hege Avsnes
HA
Seeberg
Erling
E
Rollag
Halvor
H
D001483:Base Sequence; D002453:Cell Cycle; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000472:pathogenicity* / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D010084:Oxidation-Reduction; D014498:Uracil / Q000378:metabolism; D014779:Virus Replication
D004279:DNA, Viral; D014498:Uracil; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase