Homologous DNA recombination in vertebrate cells

Sonoda, Eiichiro; Takata, Minoru; Yamashita, Yukiko; Morrison, Ciarán; Takeda, Shunichi

doi:10.1073/pnas.111006398

Cited by 140 publications

(88 citation statements)

References 117 publications

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“…Xrcc3 is one of five paralogues of Rad51 found in mammalian cells (Table 1). All five Rad51 paralogues were recently shown, by cytological methods, to be important for Rad51 assembly after x-ray treatment of chicken DT40 cells (82)(83)(84). This led Takeda and colleagues to propose that the five may function together as a single mediator complex.…”

Section: Reca-like Recombinases Assemble On Single-strand Dna (Ssdna)mentioning

confidence: 99%

Assembly of RecA-like recombinases: Distinct roles for mediator proteins in mitosis and meiosis

Gasior

Olivares

Ear

et al. 2001

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

160

125

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Members of the RecA family of recombinases from bacteriophage T4, Escherichia coli, yeast, and higher eukaryotes function in recombination as higher-order oligomers assembled on tracts of single-strand DNA (ssDNA). Biochemical studies have shown that assembly of recombinase involves accessory factors. These studies have identified a class of proteins, called recombination mediator proteins, that act by promoting assembly of recombinase on ssDNA tracts that are bound by ssDNA-binding protein (ssb). In the absence of mediators, ssb inhibits recombination reactions by competing with recombinase for DNA-binding sites. Here we briefly review mediated recombinase assembly and present results of new in vivo experiments. Immuno-double-staining experiments in Saccharomyces cerevisiae suggest that Rad51, the eukaryotic recombinase, can assemble at or near sites containing ssb (replication protein A, RPA) during the response to DNA damage, consistent with a need for mediator activity. Correspondingly, mediator gene mutants display defects in Rad51 assembly after DNA damage and during meiosis, although the requirements for assembly are distinct in the two cases. In meiosis, both Rad52 and Rad55͞57 are required, whereas either Rad52 or Rad55͞57 is sufficient to promote assembly of Rad51 in irradiated mitotic cells. Rad52 promotes normal amounts of Rad51 assembly in the absence of Rad55 at 30°C but not 20°C, accounting for the cold sensitivity of rad55 null mutants. Finally, we show that assembly of Rad51 is induced by radiation during S phase but not during G1, consistent with the role of Rad51 in repairing the spontaneous damage that occurs during DNA replication.H omologous recombination reactions promote repair of DNA ends formed by double-strand breaks (DSBs) and by replication fork collapse. Recombinational repair also allows cells to replicate past DNA lesions that block the progress of DNA polymerase. In phage T4, recombination is critical for initiating replication. In eukaryotes, homologous recombination is critical for accurate reductional segregation of chromosomes during meiosis. Finally, in prokaryotes, recombination allows horizontal transfer of alleles among and between bacteria and phage.At the center of homologous recombination are the recombinases, proteins that promote the formation of heteroduplex DNA. Of particular importance are the recombinases of the RecA family, including RecA in eubacteria, RadA in archea, Rad51 and Dmc1 in eukaryea, and the bacteriophage T4 UvsX protein.RecA-Like Recombinases Assemble on Single-Strand DNA (ssDNA).

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Section: Reca-like Recombinases Assemble On Single-strand Dna (Ssdna)mentioning

confidence: 99%

Assembly of RecA-like recombinases: Distinct roles for mediator proteins in mitosis and meiosis

Gasior

Olivares

Ear

et al. 2001

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

160

125

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“…3 The basic HR pathway is highly conserved throughout eukaryotes, with most of the known gene products involved in yeast HR having functional homologs in higher eukaryotes. 9,10 The first step of HR involves processing of the DSB such that the 5'-ends of the DNA duplex that flank the DSB are nucleolytically processed to generate long, 3' single-stranded tails. The processed DSB ends are initially bound by the single strand DNA binding protein, RPA.…”

Section: Introductionmentioning

confidence: 99%

Opening the DNA repair toolbox: Localization of DNA double strand breaks to the nuclear periphery

Oza¹,

Peterson²

2010

Cell Cycle

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E fficient repair of DNA double strand breaks is essential for cells to avoid increased mutation rates, genomic instability, and even cell death. Consequently, cells have evolved multiple mechanisms for rapidly repairing these DNA lesions, including error-free homologous recombination as well as error-prone pathways such as nonhomologous end joining. What happens to DSBs that are repaired inefficiently or not at all? Recently, several studies in budding yeast have shown that these more recalcitrant DSBs are localized to the nuclear periphery through interactions between the nuclear envelope protein, Mps3, and proteins associated with DSB chromatin. Why these DSBs are tethered to the nuclear periphery is still not clear, though the current view is that alternative repair pathways may be activated at the periphery in a final attempt to repair the lesion. In this Extra View, we discuss these recent reports, and we show that the Est1 component of the telomerase machinery plays an essential role in anchoring DSB chromatin to the nuclear envelope protein, Mps3.

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“…The technique is highly successful when combined with a selection system in a cell system like embryonic stem cells, but is not successful for targeted therapeutic gene alteration in somatic cells. [1][2][3][4] Thus, alternative approaches have aimed to specifically target and alter chromosomal DNA with smaller structures. For targeting approaches without sequence constraint, short DNA fragments, 5 and modified or phosphothioate stabilized DNA oligonucleotides have been explored.…”

Section: Introductionmentioning

confidence: 99%

Branched oligonucleotides induce in vivo gene conversion of a mutated EGFP reporter

Olsen¹,

McKeen

Krauß³

2003

Gene Ther

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UKBranched oligonucleotides (b-oligonucleotides) based on a novel branching monomer were used for site-specific sequence alteration in vivo. With a stable integrated mutated enhanced green fluorescent protein (EGFP) template in Chinese hamster ovary cells, up to 0.1% EGFP-positive cells were counted after transfection with b-oligonucleotides. The presence of EGFP protein in converted cells was demonstrated by anti-EGFP immunocytochemistry. Genomic sequencing of converted cells showed in 40% of the analysed clones the corrected wild-type codon, while 9.3% of the sequences showed a corrected wild-type sequence and an additional collateral mutation. Despite the stable corrected genomic locus, converted cells entered selective apoptosis after 3-6 days. The cell line Irs-1 that is deficient in the homologous recombination pathway showed a reduced frequency of boligonucleotide-induced site-specific sequence conversion. The reduced conversion rates in the mutant cell line could be partly rescued by complementation with XRCC2 cDNA.

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Homologous DNA recombination in vertebrate cells

Cited by 140 publications

References 117 publications

Assembly of RecA-like recombinases: Distinct roles for mediator proteins in mitosis and meiosis

Assembly of RecA-like recombinases: Distinct roles for mediator proteins in mitosis and meiosis

Opening the DNA repair toolbox: Localization of DNA double strand breaks to the nuclear periphery

Branched oligonucleotides induce in vivo gene conversion of a mutated EGFP reporter

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