Replication of herpes simplex virus type 1 DNA is inhibited in a temperature-sensitive mutant of BHK-21 cells lacking RCC1 (regulator of chromosome condensation) and virus DNA remains linear.
tsBN2, a temperature-sensitive (ts) growth mutant of the hamster cell line BHK-21, has a point mutation in the RCC1 (regulator of chromosome condensation) gene, and prematurely enters mitosis at 39.5 degrees C, a nonpermissive temperature. In this mutant at 39.5 degrees C infectious progeny of herpes simplex virus type 1 (HSV-1) was not produced and replication of HSV-1 DNA was inhibited. HSV-1 DNA from virus particles is normally circularized upon infection, and circularized HSV-1 DNA molecules can serve as template for DNA replication. In tsBN2 at 39.5 degrees C, HSV-1 DNA appeared to remain linear after infection, suggesting the obstruction of HSV-1 DNA circularization, which could account for failure of HSV-1 DNA replication. In transient replication assays performed in tsBN2 at 39.5 degrees C, through superinfection with HSV-1 helper virus, there was no evidence of replication of circular DNA of the hybrid plasmid containing the HSV-1 replication origin. Production of mRNAs of HSV-1 early genes required for HSV-1 DNA replication was decreased in tsBN2 at 39.5 degrees C. Therefore, RCC1 was assumed to be involved in the formation of an HSV-1 DNA configuration suitable for replication (that is circularization) and the supply of proteins required for replication of the circularized HSV-1 DNAs.
Umene
K
K
Department of Virology, Faculty of Medicine, Kyushu University 60, Fukuoka, Japan.
Nishimoto
T
T
D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D006224:Cricetinae; D004261:DNA Replication; D004279:DNA, Viral; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D010957:Plasmids; D017354:Point Mutation; D012333:RNA, Messenger; D012367:RNA, Viral; D018741:Replication Origin; D013696:Temperature; D014158:Transcription, Genetic; D014779:Virus Replication
D018797:Cell Cycle Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; C062521:RCC1 protein, human; D012333:RNA, Messenger; D012367:RNA, Viral; D005090:Exodeoxyribonucleases; D043211:Exodeoxyribonuclease V