C-1027-induced alterations in Epstein-Barr viral DNA replication in latently infected cultured human Raji cells: Relationship to DNA damage
McHugh, MM; Beerman TA
| HERO ID | 651747 |
|---|---|
| In Press | No |
| Year | 1999 |
| Title | C-1027-induced alterations in Epstein-Barr viral DNA replication in latently infected cultured human Raji cells: Relationship to DNA damage |
| Authors | McHugh, MM; Beerman TA |
| Journal | Biochemistry |
| Volume | 38 |
| Issue | 21 |
| Page Numbers | 6962-6970 |
| Abstract | This study is the first detailing drug-induced changes in EBV DNA replication intermediates (RIs). Both EBV replication inhibition and damage induction were studied in latently infected human Raji cells treated with the enediyne DNA strand-scission agent C-1027. Analysis of RIs on two-dimensional agarose gels revealed a rapid loss in the EBV bubble arc. When elongation of nascent chains was blocked by aphidicolin, this loss was inhibited, suggesting that C-1027-induced disappearance of RIs was related to maturation of preformed replication molecules in the absence of initiation of new RIs. C-1027 damage to EBV DNA was limited at concentrations where loss of the bubble arc was nearly complete, and none was detected within the replicating origin (ori P)-containing fragment, indicating that replication inhibition occurred in trans. By contrast, the non-nuclear mitochondrial genome was insensitive to replication inhibition but highly sensitive to damage induced by C-1027. C-1027-induced trans inhibition of nuclear but not mitochondrial DNA replication is consistent with a cell cycle checkpoint response to a DNA-damaging agent. EBV replication and Raji cell growth were inhibited at equivalent C-1027 doses. |
| Doi | 10.1021/bi9903143 |
| Pmid | 10346918 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Antibiotics; Aminoglycoside PHARMACOLOGY; Antineoplastic PHARMACOLOGY; Cell Nucleus DRUG EFFECTS; Cell Nucleus GENETICS; Cell Nucleus VIROLOGY; DNA Damage; DNA Replication DRUG EFFECTS; DNA; Mitochondrial DRUG EFFECTS; Viral DRUG EFFECTS; Electrophoresis; Gel; Two-Dimensional; Growth Inhibitors PHARMACOLOGY; Herpesvirus 4; Human DRUG EFFECTS; Human GENETICS; Human PHYSIOLOGY; Human; Mitochondria DRUG EFFECTS; Mitochondria GENETICS; Mitochondria VIROLOGY; Support; U.S.Gov't; P.H.S.; Transcription; Genetic DRUG EFFECTS; Tumor Cells; Cultured DRUG EFFECTS; Cultured PATHOLOGY; Cultured VIROLOGY; Virus Latency DRUG EFFECTS; Virus Replication DRUG EFFECTS; *Aminoglycosides; Anti-Bacterial Agents/*pharmacology; Antibiotics, Antineoplastic/*pharmacology; Cell Nucleus/drug effects/genetics/virology; *DNA Damage; DNA Replication/*drug effects; DNA, Mitochondrial/drug effects; DNA, Viral/*drug effects; Electrophoresis, Gel, Two-Dimensional; Enediynes; Growth Inhibitors/pharmacology; Herpesvirus 4, Human/drug effects/*genetics/physiology; Humans; Mitochondria/drug effects/genetics/virology; Transcription, Genetic/drug effects; Tumor Cells, Cultured/drug effects/pathology/virology; Virus Latency/drug effects; Virus Replication/drug effects; 0 (Aminoglycosides); 0 (Anti-Bacterial Agents); 0 (Antibiotics, Antineoplastic); 0 (DNA, Mitochondrial); 0 (DNA, Viral); 0 (Enediynes); 0 (Growth Inhibitors); 120177-69-7 (c 1027) |
| Is Qa | No |