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Warren Masker, PhDWarren Masker, PhD

 

Professor, Biochemistry

Telephone:  215-707-3973

Fax:  215-707-7536

Email: wmasker@temple.edu

 

 

Department of Biochemistry

 

Educational Background:

 

Department of Physics and Astronomy
University of Rochester
Rochester, New York

 

Department of Radiation Biology and Biophysics
University of Rochester
Rochester, New York

 

Department of Biological Sciences
Stanford University
Palo Alto, California

 

Department of Biological Chemistry
Harvard Medical School
Boston, Massachusetts

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Research Interests:

 

Our laboratory studies the biochemistry of how normally accurate molecular mechanisms sometimes lead to mutations during the replication or repair of DNA. Of particular interest is the mechanism by which deletions take place between directly repeated sequences of DNA. A second area of investigation is the question of how double strand breaks in DNA are repaired and why repair of these breaks is frequently accompanied by genetic rearrangements in the vicinity of the break. Our approach to these problems has been to use one of the simplest available DNA replication systems, that of bacteriophage T7, as a model system. Good in vitro systems have been developed to carry out most of the steps of T7 DNA replication, recombination, and repair. By packaging DNA in a second in vitro reaction a high yield of infective phage can be produced from DNA recovered from the DNA replication or repair reactions. The geneotype of these phage reflect mutational events that took place during the prior in vitro reactions.

 

To study deletion in T7 we interrupted the ligase gene with an insert of nonsense DNA sequence that is bracketed by direct repeats. The insert inactivates the gene and renders the phage incapable of growth on a selective host. Deletion between the direct repeats eliminates the insert and allows normal growth on the selective host. This system allows us to perform either in vivo or in vitro deletion studies. This system is currently being used to determine why a double strand break placed between the direct repeats markedly increases the frequency of deletion between the repeats. We are investigating the possibility that errors during recombination lead to deletion between direct repeats and that repair of double strand breaks via recombination may sometimes lead to deletion if the double strand break forms near a pair of direct repeats.

 

A second project in our laboratory deals directly with how double strand breaks are repaired. In T7 most double strand breaks are repaired via recombination with homologous DNA molecules present in the same cell or reaction. These recombinational repair events proceed without normal DNA replication and, therefore, are not the result of formation of new replication forks via invasion of a partial genome into an intact homologue. We have developed an in vitro system for repair of double strand breaks in T7 that is independent of the packaging system and used this to show that molecules of donor DNA are physically incorporated into a gap formed at the site of the double strand break. Currently we are attempting to determine the exact mechanism of this type of repair and to identify the roles of enzymes involved in double strand break repair in T7.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

11222583. Yu M, Masker W, T7 single strand DNA binding protein but not T7 helicase is required for DNA double strand break repair. J Bacteriol 183:6(1862-9)2001 Mar

10792729. Lai YT, Masker W, Repair of double-strand breaks by incorporation of a molecule of homologous DNA. Mol Microbiol 36:2(437-46)2000 Apr

10629177. Lai YT, Masker W, Visualization of repair of double-strand breaks in the bacteriophage T7 genome without normal DNA replication. J Bacteriol 182:2(327-36)2000 Jan

9829927. Lai YT, Masker W, In vitro repair of gaps in bacteriophage T7 DNA. J Bacteriol 180:23(6193-202)1998 Dec

9268018. Yang Y, Masker W, Double-strand breaks increase the incidence of genetic deletion associated with intermolecular recombination in bacteriophage T7. Mol Gen Genet 255:3(277-84)1997 Jul

8692197. Yang Y, Masker W, Instability of repeated dinucleotides in bacteriophage T7 genomes. Mutat Res 354:1(113-27)1996 Jul 5

8569789. Yang Y, Masker W, Deletion during recombination in bacteriophage T7. Mutat Res 349:1(21-32)1996 Jan 17

7928950. Kong D, Masker W, Deletion between direct repeats in T7 DNA stimulated by double-strand breaks. J Bacteriol 176:19(5904-11)1994 Oct

7688091. Scearce LM, Masker W, Deletion between direct repeats in bacteriophage T7 gene 1.2. Mutat Res 288:2(301-10)1993 Aug

8463301. Kong D, Masker W, Deletion between directly repeated DNA sequences measured in extracts of bacteriophage T7-infected Escherichia coli. J Biol Chem 268:11(7721-7)1993 Apr 15

7680757. Masker W, Crissey MA, The effect of the 3'-->5' exonuclease of T7 DNA polymerase on frameshifts and deletions. Mutat Res 301:4(235-41)1993 Apr

1370985. Pierce JC, Masker W, Frameshift mutagenesis in bacteriophage T7. Mutat Res 281:2(81-7)1992 Feb

1309515. Masker W, In vitro repair of double-strand breaks accompanied by recombination in bacteriophage T7 DNA. J Bacteriol 174:1(155-60)1992 Jan

1861982. Pierce JC, Kong D, Masker W, The effect of the length of direct repeats and the presence of palindromes on deletion between directly repeated DNA sequences in bacteriophage T7. Nucleic Acids Res 19:14(3901-5)1991 Jul 25

1846152. Scearce LM, Pierce JC, McInroy B, Masker W, Deletion mutagenesis independent of recombination in bacteriophage T7. J Bacteriol 173:2(869-78)1991 Jan

2549373. Pierce JC, Masker W, Genetic deletions between directly repeated sequences in bacteriophage T7. Mol Gen Genet 217:2-3(215-22)1989 Jun

3050148. Pierce JC, Masker WE, A single-base change in gene 10 of bacteriophage T7 permits growth on Shigella sonnei. J Virol 62:11(4369-71)1988 Nov

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