Cell division transforms mutagenic lesions into deletion-recombinagenic lesions in yeast cells

Galli, Alvaro; Schiestl, Robert H.

doi:10.1016/s0027-5107(99)00097-4

Cited by 51 publications

(43 citation statements)

References 55 publications

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“…We found that 50 and 100 Gray (Gy) of gamma radiation had no significant effect on the viability of G2-arrested cells and only a small effect on the viability of G1-arrested cells. In most previous studies, the viability of G2-arrested cells is unaffected by doses of radiation of 100 Gy or less; the viability of G1-arrested cells is usually reduced about 2-fold by doses of 100 Gy (20)(21)(22). In agreement with these previous studies, gamma rays induced mitotic recombination in both G1-and G2-arrested cells.…”

Section: Effect Of Gamma Irradiation On Cell Viability and The Frequesupporting

confidence: 86%

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Mitotic gene conversion events induced in G1-synchronized yeast cells by gamma rays are similar to spontaneous conversion events

Lee

Petes

2010

Proc. Natl. Acad. Sci. U.S.A.

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In a previous study, we mapped spontaneous mitotic reciprocal crossovers (RCOs) in a 120-kb interval of chromosome V of Saccharomyces cerevisiae. About three-quarters of the crossovers were associated with gene conversion tracts. About 40% of these conversion tracts had the pattern expected as a consequence of repair of a double-stranded DNA break (DSB) of an unreplicated chromosome. We test this hypothesis by examining the crossovers and gene conversion events induced by gamma irradiation in G1-and G2-arrested diploid yeast cells. The gene conversion patterns of G1-irradiated cells (but not G2-irradiated cells) mimic conversion events associated with spontaneous RCOs, confirming our previous conclusion that many spontaneous crossovers are initiated by a DSB on an unreplicated chromosome.homologous recombination | DNA breaks | Saccharomyces cerevisae | loss of heterozygosity H omologous mitotic recombination is an efficient method of repairing double-stranded breaks (DSBs) in the yeast Saccharomyces cerevisiae and other organisms (1). Although mitotic recombination was described in Drosophila more than 70 years ago (2), many of the basic properties of mitotic recombination are not understood. The chromosomes resulting from a mitotic recombination event are segregated into two daughter cells and one problem is that most analytic methods select for only one of the cells containing the recombinant chromosomes.A method for selecting both daughter cells with the products expected from reciprocal crossing over (RCO) is shown in Fig. 1. A diploid yeast strain is constructed in which one copy of chromosome V has an ochre mutation in the CAN1 gene (can1-100); in the absence of an ochre suppressor, such strains are resistant to canavanine. On the other homologue, the CAN1 gene has been replaced by SUP4-o, a gene encoding an ochre-suppressing tRNA. The diploid is also homozygous for the ade2-1 ochre mutation. Yeast strains containing the ade2-1 allele without a nonsense suppressor are Ade − and form red colonies as a result of accumulation of red precursor to adenine (3). In the diploid depicted in Fig. 1, because of the presence of the SUP4-o gene, the cells are canavanine-sensitive, Ade + , and form white colonies.A RCO between the centromere of chromosome V and the can1-100/SUP4-o markers will result in two Can R daughter cells that will subsequently grow to form a red/white sectored Can R colony (4). As a consequence of the RCO, polymorphisms distal to the crossover point become homozygous in the two sectors, whereas polymorphisms proximal to the exchange retain heterozygosity ( Fig.

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Section: Effect Of Gamma Irradiation On Cell Viability and The Frequesupporting

confidence: 86%

“…Single-stranded nicks are recombinogenic in yeast (29). Replication of nicked DNA molecules can give rise to a recombinogenic DSB (22,30). In addition, nicked or gapped DNA molecules can stimulate conversion directly, without being converted to a DSB (31)(32)(33).…”

Section: Effect Of Gamma Irradiation On Cell Viability and The Frequementioning

confidence: 99%

Mitotic gene conversion events induced in G1-synchronized yeast cells by gamma rays are similar to spontaneous conversion events

Lee

Petes

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Intermediates in NER include nicks and short gaps, which have been proposed as initiators of recombination (see below) either directly or in relation to stalled replication forks. 8,26,27 The nicks and gaps created by NER could be recombinogenic with or without being processed to DSBs (Fig. 1B and C).…”

Section: Genetic Recombinationmentioning

confidence: 99%

“…The resulting gapped DNA at stalled forks or subsequent DSBs could be rescued through homologous recombination. 8,26 UV-Induced Recombination at G 1 Suggests A DSB Intermediate Allelic recombination (recombination between homologous chromosomes) can homologous recombination. Early recombination models were based on ss breaks, not DSBs, as initiating events.…”

Section: Genetic Recombinationmentioning

confidence: 99%

Understanding the origins of UV-induced recombination through manipulation of sister chromatid cohesion

Covo

Westmoreland

et al. 2012

Cell Cycle

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“…In contrast to irradiation which produces a wide spectrum of DNA lesions [Frankenberg-Schwager, 1990], exposure to ENU mainly causes alkylation of DNA at the Nand O-positions, resulting predominantly in base substitution mutations [Shibuya and Morimoto, 1993]. ENU can also induce DNA lesions attributable to either fragile alkali-labile sites [Friedberg et al, 2006] or the conversion of alkylation-induced DNA damage into double-strand breaks during DNA replication [Galli and Schiestl, 1999]. However, these lesions are far less complex and frequent than radiation-induced DSBs.…”

Section: Introductionmentioning

confidence: 99%

Paternal exposure to ethylnitrosourea results in transgenerational genomic instability in mice

Dubrova

Hickenbotham

Glen

et al. 2008

Environ and Mol Mutagen

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Recent data show that the effects of ionising radiation are not restricted to the directly exposed parental germ cells, but can also manifest in their non-exposed offspring, resulting in elevated mutation rates and cancer predisposition. The mechanisms underlying these transgenerational changes remain poorly understood. One of the most important steps in elucidating these mechanisms is to investigate the initial cellular events that trigger genomic instability. Here we have analysed the effects of paternal treatment by ethylnitrosourea, an alkylating agent which is known to form specific types of DNA adducts, on the transgenerational effects in the first-generation (F 1 ) offspring of exposed CBA/Ca and BALB/c male mice. Mutation rates at two expanded simple tandem repeat loci were significantly elevated in the F 1 germline of both strains. Pre-and post-meiotic exposures resulted in similar increases in mutation rate in the F 1 germline. Within each strain mutation rates were equally elevated in the germline of male and female F 1 offspring of the directly exposed males. The results of our study suggest that transgenerational instability is not attributed to a specific sub-set of DNA lesions, such as double strand breaks, and is most probably triggered by a stress-like response to a generalised DNA damage.2

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Cell division transforms mutagenic lesions into deletion-recombinagenic lesions in yeast cells

Cited by 51 publications

References 55 publications

Mitotic gene conversion events induced in G1-synchronized yeast cells by gamma rays are similar to spontaneous conversion events

Mitotic gene conversion events induced in G1-synchronized yeast cells by gamma rays are similar to spontaneous conversion events

Understanding the origins of UV-induced recombination through manipulation of sister chromatid cohesion

Paternal exposure to ethylnitrosourea results in transgenerational genomic instability in mice

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