Conditional Lethality of Null Mutations in RTH1 That Encodes the Yeast Counterpart of a Mammalian 5′- to 3′-Exonuclease Required for Lagging Strand DNA Synthesis in Reconstituted Systems
Open Access
- 1 March 1995
- journal article
- Published by Elsevier BV
- Vol. 270 (9), 4193-4196
- https://doi.org/10.1074/jbc.270.9.4193
Abstract
A 5'- to 3'-exonuclease of about 45 kDa has been purified from various mammalian sources and shown to be required for the completion of lagging strand synthesis in reconstituted DNA replication systems. RTH1 encodes the yeast Saccharomyces cerevisiae counterpart of the mammalian enzyme. To determine the in vivo biological role of RTH1-encoded 5'- to 3'-exonuclease, we have examined the effects of an rth1 delta mutation on various cellular processes. rth1 delta mutants grow poorly at 30 degrees C, and a cessation in growth occurs upon transfer of the mutant to 37 degrees C. At the restrictive temperature, the rth1 delta mutant exhibits a terminal cell cycle morphology similar to that of mutants defective in DNA replication, and levels of spontaneous mitotic recombination are elevated in the rth1 delta mutant even at the permissive temperature. The rth1 delta mutation does not affect UV or gamma-ray sensitivity but enhances sensitivity to the alkylating agent methyl methanesulfonate. The role of RTH1 in DNA replication and in repair of alkylation damage is discussed.Keywords
This publication has 14 references indexed in Scilit:
- Enzymatic completion of mammalian lagging-strand DNA replication.Proceedings of the National Academy of Sciences of the United States of America, 1994
- Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair.Genes & Development, 1994
- Human xeroderma pigmentosum group G gene encodes a DNA endonucleaseNucleic Acids Research, 1994
- DNA REPAIR GENES AND PROTEINS OF SACCHAROMYCES CEREVISIAEAnnual Review of Genetics, 1993
- Yeast excision repair gene RAD2 encodes a single-stranded DNA endonucleaseNature, 1993
- Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2Nature, 1993
- [12] One-step gene disruption in yeastMethods in enzymology, 1983
- A Conditional Lethal Mutant of Escherichia coli K12 Defective in the 5′ → 3′ Exonuclease Associated with DNA Polymerase IProceedings of the National Academy of Sciences of the United States of America, 1974
- Genetic and enzymatic characterization of a conditional lethal mutant of Escherichia coli K12 with a temperature-sensitive DNA ligaseJournal of Molecular Biology, 1973
- Genetic control of the cell division cycle in yeastExperimental Cell Research, 1971