Homologous genetic recombination as an intrinsic dynamic property of a DNA structure induced by RecA/Rad51-family proteins: A possible advantage of DNA over RNA as genomic material

Shibata, Takehiko; Nishinaka, Taro; Mikawa, Tsutomu; Aihara, Hideki; Kurumizaka, Hitoshi; Yokoyama, Shigeyuki; Ito, Yutaka

doi:10.1073/pnas.111005198

Cited by 58 publications

(44 citation statements)

References 107 publications

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“…We previously showed that the recognition of homology in duplex DNA by the single strand in the Rad51 filament requires the breathing of base pairs, particularly A⅐T base pairs, in the duplex DNA (19). That mechanism of recognition plus the ability of Rad51 to form paranemic joints implies that the nucleoprotein filament provides an extended catalytic surface that can promote breathing and subsequent homologous recognition anywhere along the length of the DNA molecules involved.…”

Section: Mechanism Of Recognition Of Homologymentioning

confidence: 99%

“…18). Solution of the structure of the single strand has shown that the bases, whose axial spacing is 50% greater than in B-form DNA, are stacked alternately with the deoxyribose moieties of the phosphodiester backbone, a configuration that links the angular displacement of bases to a change in the pucker of the sugar (19). Recent studies of human Rad51 indicate that the filament formed on single-stranded DNA provides a catalytic surface, which, on collision with duplex DNA, promotes the opening of base pairs to check for homology at the point of contact anywhere along the filament (20).…”

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confidence: 99%

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The synaptic activity of HsDmc1, a human recombination protein specific to meiosis

Gupta

Golub

et al. 2001

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

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Human Dmc1 protein, a meiosis-specific homolog of Escherichia coli RecA protein, has previously been shown to promote DNA homologous pairing and strand-exchange reactions that are qualitatively similar to those of RecA protein and Rad51. Human and yeast Rad51 proteins each form a nucleoprotein filament that is very similar to the filament formed by RecA protein. However, recent studies failed to find a similar filament made by Dmc1 but showed instead that this protein forms octameric rings and stacks of rings. These observations stimulated further efforts to elucidate the mechanism by which Dmc1 promotes the recognition of homology. Dmc1, purified to a state in which nuclease and helicase activities were undetectable, promoted homologous pairing and strand exchange as measured by fluorescence resonance energy transfer (FRET). Observations on the intermediates and products, which can be distinguished by FRET assays, provided direct evidence of a three-stranded synaptic intermediate. The effects of helix stability and mismatched base pairs on the recognition of homology revealed further that human Dmc1, like human Rad51, requires the preferential breathing of A⅐T base pairs for recognition of homology. We conclude that Dmc1, like human Rad51 and E. coli RecA protein, promotes homologous pairing and strand exchange by a ''synaptic pathway'' involving a three-stranded nucleoprotein intermediate, rather than by a ''helicase pathway'' involving the separation and reannealing of DNA strands.T wo kinds of macromolecular protein structures play prominent roles in homologous genetic recombination: toroids and filaments. Among the toroidal structures, the best understanding of the relation of function to structure exists for Escherichia coli RuvB protein, which forms a hexameric ATPase͞helicase. Two such hexameric rings, interacting with RuvA protein, drive the migration of Holliday structures, the 4-fold branched DNA intermediate formed after initial synapsis and processing have occurred. The consequence of this driven migration is the reciprocal exchange of a pair of like strands between two duplex molecules (1). Rings are also formed by the exonuclease of phage (2), the Erf protein of phage P22 (3), and human Rad52 protein (4, 5). On the basis of the crystal structure of toroidal exonuclease, Kovall and Matthews suggested a mechanistic explanation of the high processivity of this enzyme (2).Some recombination proteins form both rings and filaments: the ␤ protein of phage forms large rings and left-handed helical filaments (6). ␤ protein promotes annealing of complementary single strands (7,8) and migration of a single-stranded branch (9). This protein, which does not hydrolyze ATP, binds more strongly to the product of its annealing activity, which may help to explain how it drives branch migration (10), but there are no correlations of structure with function that help us to understand the role of either the rings or the left-handed filaments. RecT protein, the product of a cryptic prophage in E. coli and a functional ...

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Section: Mechanism Of Recognition Of Homologymentioning

confidence: 99%

mentioning

confidence: 99%

The synaptic activity of HsDmc1, a human recombination protein specific to meiosis

Gupta

Golub

et al. 2001

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

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“…Takehiko Shibata discussed NMR studies revealing the basis for the extended structure of ssDNA within the filaments of RecA or its yeast homolog Rad51 (55). Charles Radding reviewed the current understanding of the most critical and still mysterious step of recombinational repair, the RecA-catalyzed homology search with subsequent strand exchange.…”

Section: Homologous Recombination In Phage T4mentioning

confidence: 99%

DNA replication meets genetic exchange: Chromosomal damage and its repair by homologous recombination

Kuzminov

2001

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

198

126

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Proceedings of the National Academy of Sciences Colloquium on the roles of homologous recombination in DNA replication are summarized. Current findings in experimental systems ranging from bacteriophages to mammalian cell lines substantiate the idea that homologous recombination is a system supporting DNA replication when either the template DNA is damaged or the replication machinery malfunctions. There are several lines of supporting evidence: (i) DNA replication aggravates preexisting DNA damage, which then blocks subsequent replication; (ii) replication forks abandoned by malfunctioning replisomes become prone to breakage; (iii) mutants with malfunctioning replisomes or with elevated levels of DNA damage depend on homologous recombination; and (iv) homologous recombination primes DNA replication in vivo and can restore replication fork structures in vitro. The mechanisms of recombinational repair in bacteriophage T4, Escherichia coli, and Saccharomyces cerevisiae are compared. In vitro properties of the eukaryotic recombinases suggest a bigger role for single-strand annealing in the eukaryotic recombinational repair.

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“…Following homologous pairing of the invading DNA strand with its double-stranded counterpart, RecA protein initiates the exchange of DNA strands that results in a heteroduplex DNA with the formation of a D-loop (DasGupta et al, 1980). Currently there is no established mechanism to explain how RecA allows the invading DNA chain to displace one of the strands of fully base-paired double-stranded DNA (Shibata et al, 2001). The most important feature of this process for our purpose is that RecA-mediated exchange of DNA strands can tolerate, at a low frequency, DNA lesions or mismatched base pairs during pairing (Bianchi and Radding, 1983;Bazemore et al, 1997) and thereby alter base pairs in a targeted sequence.…”

Section: Introductionmentioning

confidence: 99%

RecA-Mediated, Targeted Mutagenesis in Zebrafish

Cui

Yang

Kaufman

et al. 2003

Marine Biotechnology

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Abstract:We have evaluated the efficacy of RecA, a prokaryotic protein involved with homologous recombination, to direct site-specific mutagenesis in zebrafish embryos. For this we coinjected a vector containing a mutated enhanced green fluorescent protein (EGFP) gene plus 236-nucleotide corrective single-stranded DNAs coated with RecA into 1-cell zebrafish embryos. Twenty-hours after fertilization, about 5% to 20% of injected embryos showed EGFP expression in 1 or more cells when RecA-coated corrective DNAs were used, but not when RecA was omitted. Mutated EGFP genes with 1-bp insertions or deletions were inefficiently activated, whereas those with 7-bp insertions were activated about 4-fold more efficiently. RecA-coated template strand had a higher efficiency than its complementary strand in activation of EGFP expression. Prior irradiation of the embryos with UV light enhanced RecA-mediated restoration of gene activity, suggesting that the effects we observed were augmented by one or more factors of zebrafish DNA repair systems.

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Homologous genetic recombination as an intrinsic dynamic property of a DNA structure induced by RecA/Rad51-family proteins: A possible advantage of DNA over RNA as genomic material

Cited by 58 publications

References 107 publications

The synaptic activity of HsDmc1, a human recombination protein specific to meiosis

The synaptic activity of HsDmc1, a human recombination protein specific to meiosis

DNA replication meets genetic exchange: Chromosomal damage and its repair by homologous recombination

RecA-Mediated, Targeted Mutagenesis in Zebrafish

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