Analysis of Rev1p and Pol zeta in mitochondrial mutagenesis suggests an alternative pathway of damage tolerance.
Ultraviolet light is a potent DNA damaging agent that induces bulky lesions in DNA which block the replicative polymerases. In order to ensure continued DNA replication and cell viability, specialized translesion polymerases bypass these lesions at the expense of introducing mutations in the nascent DNA strand. A recent study has shown that the N-terminal sequences of the nuclear translesion polymerases Rev1p and Pol zeta can direct GFP to the mitochondrial compartment of Saccharomyces cerevisiae. We have investigated the role of these polymerases in mitochondrial mutagenesis. Our analysis of mitochondrial DNA point mutations, microsatellite instability, and the spectra of mitochondrial mutations indicate that these translesion polymerases function in a less mutagenic pathway in the mitochondrial compartment than they do in the nucleus. Mitochondrial phenotypes resulting from the loss of Rev1p and Pol zeta suggest that although these polymerases are responsible for the majority of mitochondrial frameshift mutations, they do not greatly contribute to mitochondrial DNA point mutations. Analysis of spontaneous mitochondrial DNA point mutations suggests that Pol zeta may play a role in general mitochondrial DNA maintenance. In addition, we observe a 20-fold increase in UV-induced mitochondrial DNA point mutations in rev deficient strains. Our data provides evidence for an alternative damage tolerance pathway that is specific to the mitochondrial compartment.
Kalifa
Lidza
L
Department of Biology, University of Rochester, Rochester, NY 14627, United States.
Sia
Elaine A
EA
D004249:DNA Damage; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000378:metabolism*; D017354:Point Mutation; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
D004271:DNA, Fungal; D004259:DNA-Directed DNA Polymerase; D009713:Nucleotidyltransferases; D029701:Saccharomyces cerevisiae Proteins; C425929:DNA polymerase zeta; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases
J Bacteriol. 1989 Oct;171(10):5659-67
2676986
Curr Genet. 1989 Oct;16(4):273-9
2697468
Mutat Res. 1987 Aug;179(2):167-74
3614243
J Genet. 1949 Dec;49(3):264-85
24536673
Methods Enzymol. 1991;194:3-21
2005794
Mutat Res. 2006 Mar 20;595(1-2):91-106
16337661
Mol Gen Genet. 1984;195(3):487-90
6381967
Genetics. 1971 May;68(1):21-33
17248528
J Biol Chem. 1998 Sep 11;273(37):23690-7
9726974
Methods Enzymol. 1991;194:149-65
1706458
Genetics. 1976 Feb;82(2):207-32
770231
DNA Repair (Amst). 2006 Jul 13;5(7):829-39
16730479
Mutat Res. 2000 Jun 30;451(1-2):169-85
10915871
Genetics. 1979 Jun;92(2):397-408
385449
Clin Cancer Res. 2006 Jan 15;12(2):563-8
16428501
Mol Microbiol. 2000 Aug;37(3):549-54
10931348
Curr Genet. 2000 Nov;38(4):178-87
11126776
EMBO J. 1992 Jul;11(7):2717-26
1321035
Proc Natl Acad Sci U S A. 1996 May 28;93(11):5253-7
8643562
DNA Repair (Amst). 2002 Jun 21;1(6):425-35
12509231
Mutat Res. 1979 Apr;60(2):173-80
379626
Genetics. 2005 Feb;169(2):575-82
15520252
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):250-5
10618404
Nucleic Acids Res. 1984 Nov 26;12(22):8313-8
6095195
Mol Gen Genet. 1985;200(1):80-5
3897794
Science. 1999 Jul 9;285(5425):263-5
10398605
Nature. 1999 Jun 17;399(6737):700-4
10385124
Genetics. 2002 Apr;160(4):1409-22
11973297
Nucleic Acids Res. 1982 Nov 11;10(21):6571-7
6757866
J Mol Biol. 2004 Sep 24;342(4):1115-29
15351639
Genetics. 2006 Apr;172(4):2683-8
16452144
Am J Med Genet. 2001 Spring;106(1):27-36
11579422
Philos Trans R Soc Lond B Biol Sci. 2001 Jan 29;356(1405):41-6
11205328
Science. 1996 Jun 14;272(5268):1646-9
8658138
Mol Gen Genet. 2000 Jan;262(6):1036-46
10660064
Nature. 1996 Aug 22;382(6593):729-31
8751446
Am J Med Genet. 2001 Spring;106(1):1-3
11579419