- THIS ARTICLE
- Full Text (PDF)
- Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Woodworth, D. L.
- Articles by Kreuzer, K. N.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Woodworth, D. L.
- Articles by Kreuzer, K. N.
Genetics, Vol 143, 1081-1090, Copyright © 1996
INVESTIGATIONS |
Bacteriophage T4 Mutants Hypersensitive to an Antitumor Agent That Induces Topoisomerase-DNA Cleavage Complexes
D. L. Woodworth and K. N. Kreuzer
Present address: Biology Department, Muhlenberg College, Allentown, PA 18104.
Many antitumor agents and antibiotics affect cells by interacting with type II topoisomerases, stabilizing a covalent enzyme-DNA complex. A pathway of recombination can apparently repair this DNA damage. In this study, transposon mutagenesis was used to identify possible components of the repair pathway in bacteriophage T4. Substantial increases in sensitivity to the antitumor agent m-AMSA [4'-(9-acridinyl-amino) methanesulfon-m-anisidide] were found with transposon insertion mutations that inactivate any of six T4-encoded proteins: UvsY (DNA synaptase accessory protein), UvsW (unknown function), Rnh (RNase H and 5' to 3' DNA exonuclease), {alpha}-gt ({alpha}-glucosyl transferase), gp47.1 (uncharacterized), and NrdB ({beta} subunit of ribonucleotide reductase). The role of the rnh gene in drug sensitivity was further characterized. First, an in-frame rnh deletion mutation was constructed and analyzed, providing evidence that the absence of Rnh protein causes hypersensitivity to m-AMSA. Second, the m-AMSA sensitivity of the rnh-deletion mutant was shown to require a drug-sensitive T4 topoisomerase. Third, analysis of double mutants suggested that uvsW and rnh mutations impair a common step in the recombinational repair pathway for m-AMSA-induced damage. Finally, the rnh-deletion mutant was found to be hypersensitive to UV, implicating Rnh in recombinational repair of UV-induced damage.
This article has been cited by other articles:
 |
|
 |
|
  D. T. Long and K. N. Kreuzer Regression supports two mechanisms of fork processing in phage T4 PNAS, May 13, 2008; 105(19): 6852 - 6857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Devos, S. J. Tomanicek, C. E. Jones, N. G. Nossal, and T. C. Mueser Crystal Structure of Bacteriophage T4 5' Nuclease in Complex with a Branched DNA Reveals How Flap Endonuclease-1 Family Nucleases Bind Their Substrates J. Biol. Chem., October 26, 2007; 282(43): 31713 - 31724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. W. Nelson and S. J. Benkovic The T4 Phage UvsW Protein Contains Both DNA Unwinding and Strand Annealing Activities J. Biol. Chem., January 5, 2007; 282(1): 407 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Gangisetty, C. E. Jones, M. Bhagwat, and N. G. Nossal Maturation of Bacteriophage T4 Lagging Strand Fragments Depends on Interaction of T4 RNase H with T4 32 Protein Rather than the T4 Gene 45 Clamp J. Biol. Chem., April 1, 2005; 280(13): 12876 - 12887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sabourin, J. L. Nitiss, K. C. Nitiss, K. Tatebayashi, H. Ikeda, and N. Osheroff Yeast recombination pathways triggered by topoisomerase II-mediated DNA breaks Nucleic Acids Res., August 1, 2003; 31(15): 4373 - 4384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Miller, E. Kutter, G. Mosig, F. Arisaka, T. Kunisawa, and W. Ruger Bacteriophage T4 Genome Microbiol. Mol. Biol. Rev., March 1, 2003; 67(1): 86 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. George, B. A. Stohr, D. J. Tomso, and K. N. Kreuzer The tight linkage between DNA replication and double-strand break repair in bacteriophage T4 PNAS, July 17, 2001; 98(15): 8290 - 8297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Dudas and K. N. Kreuzer UvsW Protein Regulates Bacteriophage T4 Origin-Dependent Replication by Unwinding R-Loops Mol. Cell. Biol., April 15, 2001; 21(8): 2706 - 2715. [Abstract] [Full Text]
|
|
|
|
 |
|
 Y.-J. Huang, M. M. Parker, and M. Belfort Role of Exonucleolytic Degradation in Group I Intron Homing in Phage T4 Genetics, December 1, 1999; 153(4): 1501 - 1512. [Abstract] [Full Text]
|
|
|
|
|
|
M. M. Parker, M. Belisle, and M. Belfort Intron Homing With Limited Exon Homology: Illegitimate Double-Strand-Break Repair in Intron Acquisition by Phage T4 Genetics, December 1, 1999; 153(4): 1513 - 1523. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Bebenek, L. A. Smith, and J. W. Drake Bacteriophage T4 rnh (RNase H) Null Mutations: Effects on Spontaneous Mutation and Epistatic Interaction with rII Mutations J. Bacteriol., May 15, 1999; 181(10): 3123 - 3128. [Abstract] [Full Text]
|
|
|
|
|
|
J. C. Connelly, L. A. Kirkham, and D. R. F. Leach The SbcCD nuclease of Escherichia coli is a structural maintenance of chromosomes (SMC) family protein that cleaves hairpin DNA PNAS, July 7, 1998; 95(14): 7969 - 7974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Wang and L. S. Ripley The Spectrum of Acridine Resistant Mutants of Bacteriophage T4 Reveals Cryptic Effects of the tsL141 DNA Polymerase Allele on Spontaneous Mutagenesis Genetics, April 1, 1998; 148(4): 1655 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bhagwat, L. J. Hobbs, and N. G. Nossal The 5'-Exonuclease Activity of Bacteriophage T4 RNase H Is Stimulated by the T4 Gene 32 Single-stranded DNA-binding Protein, but Its Flap Endonuclease Is Inhibited J. Biol. Chem., November 7, 1997; 272(45): 28523 - 28530. [Abstract] [Full Text] [PDF]
|
|