Ionizing Radiation Induces Microhomology-Mediated End Joining<i>in trans</i>in Yeast and Mammalian Cells

Scuric, Zorica; Chan, Cecilia Y.; Hafer, Kurt; Schiestl, Robert H.

doi:10.1667/rr1329.1

Cited by 17 publications

(12 citation statements)

References 56 publications

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“…Very nice work was recently done demonstrating that if a mammalian cell line is first irradiated and then transfected with a linearized plasmid, greater MH is used in repairing the plasmid than if the cells were not irradiated prior to transfection [65]. Similar results were observed in yeast.…”

Section: Caveats Of Dna Repair Studies To Considermentioning

confidence: 66%

Non-homologous end joining often uses microhomology: Implications for alternative end joining

Pannunzio¹,

Li²,

Watanabe³

et al. 2014

DNA Repair

111

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Artemis and PALF (also called APLF) appear to be among the primary nucleases involved in NHEJ and responsible for most nucleolytic end processing in NHEJ. About 60% of NHEJ events show an alignment of the DNA ends that uses 1 or 2 bp of microhomology (MH) between the two DNA termini. Thus, MH is a common feature of NHEJ. For most naturally-occurring human chromosomal deletions (e.g., after oxidative damage or radiation) and translocations, such as those seen in human neoplasms and as well as inherited chromosomal structural variations, MH usage occurs at a frequency that is typical of NHEJ, and does not suggest major involvement of alternative pathways that require more extensive MH. Though we mainly focus on human NHEJ at DSBs, comparison on these points to other eukaryotes, primarily S. cerevisiae, is informative.

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Section: Caveats Of Dna Repair Studies To Considermentioning

confidence: 66%

Non-homologous end joining often uses microhomology: Implications for alternative end joining

Pannunzio¹,

Li²,

Watanabe³

et al. 2014

DNA Repair

111

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show abstract

“…For example, creation of a catalytically dead Dnl4 mutant revealed an imprecise repair pathway that did not fit neatly into either c-NHEJ or MMEJ categories (Chiruvella et al 2013a). Future work to understand these pathways will be necessary, as it is now accepted that MMEJ repairs ionizing radiation damage in both yeast and mammalian cells (Scuric et al 2009). …”

Section: Alt-nhej and Mmejmentioning

confidence: 99%

Consider the workhorse: Nonhomologous end-joining in budding yeast

Emerson

Bertuch

2016

Biochem. Cell Biol.

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DNA double strand breaks (DSBs) are dangerous sources of genome instability and must be repaired by the cell. Nonhomologous end joining (NHEJ) is an evolutionarily conserved pathway to repair DSBs by direct ligation of the ends, with no requirement for a homologous template. While NHEJ is the primary DSB repair pathway in mammalian cells, conservation of the core NHEJ factors throughout eukaryotes make the pathway attractive for study in model organisms. The budding yeast, Saccharomyces cerevisiae, has been used extensively to develop a functional picture of NHEJ. In this review, we will discuss the current understanding of NHEJ in S. cerevisiae. Topics include canonical end-joining, alternative end-joining, and pathway regulation. Particular attention will be paid to the NHEJ mechanism involving core factors, including Yku70/80, Dnl4, Lif1, and Nej1, as well as the various factors implicated in the processing of the broken ends. The relevance of chromatin dynamics to NHEJ will also be discussed. This review illustrates the use of S. cerevisiae as a powerful system to understand the principles of NHEJ, as well as in pioneering the direction of the field.

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“…We also showed that restriction enzymes enhance the efficiency of NHI at non-restriction sites and that overexpression of ISceI endonuclease induces MHMR events at random genomic locations rather than being targeted to the proximity of the I-SceI-induced DSB. We further demonstrated that exposure of yeast and mammalian cells to radiation before transformation of the linearized plasmid increases the frequency of microhomology-mediated end joining (MMEJ) of the unirradiated plasmid that is in trans to radiation-induced damage (21). These previous results suggest that DSBs induce MHMR in trans at random non-targeted sites during integration of the plasmid into the genome.…”

Section: Introductionmentioning

confidence: 65%

Rad1, rad10 and rad52 Mutations Reduce the Increase of Microhomology Length during Radiation-Induced Microhomology-Mediated Illegitimate Recombination in Saccharomyces cerevisiae

Schiestl¹

2009

rare

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Illegitimate recombination can repair DNA double-strand breaks in one of two ways, either without sequence homology or by using a few base pairs of homology at the junctions. The second process is known as microhomology-mediated recombination. Previous studies showed that ionizing radiation and restriction enzymes increase the frequency of microhomology-mediated recombination in trans during rejoining of unirradiated plasmids or during integration of plasmids into the genome. Here we show that radiation-induced microhomology-mediated recombination is reduced by deletion of RAD52, RAD1 and RAD10 but is not affected by deletion of RAD51 and RAD2. The rad52 mutant did not change the frequency of radiation-induced microhomologymediated recombination but rather reduced the length of microhomology required to undergo repair during radiation-induced recombination. The rad1 and rad10 mutants exhibited a smaller increase in the frequency of radiation-induced microhomology-mediated recombination, and the radiation-induced integration junctions from these mutants did not show more than 4 bp of microhomology. These results suggest that Rad52 facilitates annealing of short homologous sequences during integration and that Rad1/Rad10 endonuclease mediates removal of the displaced 3′ single-stranded DNA ends after base-pairing of microhomology sequences, when more than 4 bp of microhomology are used. Taken together, these results suggest that radiationinduced microhomology-mediated recombination is under the same genetic control as the singlestrand annealing apparatus that requires the RAD52, RAD1 and RAD10 genes.

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Ionizing Radiation Induces Microhomology-Mediated End Joiningin transin Yeast and Mammalian Cells

Cited by 17 publications

References 56 publications

Non-homologous end joining often uses microhomology: Implications for alternative end joining

Non-homologous end joining often uses microhomology: Implications for alternative end joining

Consider the workhorse: Nonhomologous end-joining in budding yeast

Rad1, rad10 and rad52 Mutations Reduce the Increase of Microhomology Length during Radiation-Induced Microhomology-Mediated Illegitimate Recombination in Saccharomyces cerevisiae

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