Repairing a double–strand chromosome break by homologous recombination: revisiting Robin Holliday's model

Haber, James E.; Ira, Gregorz; Malkova, Anna; Sugawara, Neal

doi:10.1098/rstb.2003.1367

Cited by 69 publications

(73 citation statements)

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“…Homologous recombination (HR) appears to be universal among cellular organisms, and multiple forms, or pathways, of HR operate within individual species of bacteria (Kreuzer, 2005;Michel et al, 2001) and eukaryotes (Allers & Lichten, 2001;Aylon & Kupiec, 2004;Haber et al, 2004). Both ubiquity and mechanistic diversity are consistent with the fundamental roles HR is believed to play in supporting timely replication and partitioning of genomes.…”

Section: Introductionmentioning

confidence: 85%

“…The fact that a DSB in the donor DNA on the 59 side of the selected region generates more Pyr + recombinants than one on its 39 side suggests an asymmetry which is not intrinsic to most HR pathways in bacteria and eukaryotes (Kuzminov, 2001;Kreuzer, 2005;Aylon & Kupiec, 2004;Haber et al, 2004), and thus represents a potentially informative feature of HR in S. acidocaldarius. An even stronger asymmetry occurs in transformation of S. acidocaldarius by ssDNA: for most pyrE mutations, an oligonucleotide representing the transcribed (i.e.…”

Section: J Rockwood and Othersmentioning

confidence: 99%

“…Evidence of both reciprocal and non-reciprocal pathways of HR in Sulfolobus species has been reported: transformation of S. acidocaldarius by short oligonucleotides (Grogan & Stengel, 2008;Mao & Grogan, 2012), implies a non-reciprocal (geneconversion) pathway on mechanistic grounds, whereas integration of circular DNAs targeted by inserts of host sequence (Wagner et al, 2009) implies reciprocal strand exchange (crossing over) via the well-studied DSBR pathway (Allers & Lichten, 2001;Aylon & Kupiec, 2004;Haber et al, 2004). In attempts to detect integration via crossing over in S. acidocaldarius, we constructed an E. coli plasmid bearing a heterologous selectable marker (pyrE of S. solfataricus) separated from a non-essential region of the S. acidocaldarius chromosome providing a site for integration.…”

Section: Circularity and Orientation Of Donor Sequencesmentioning

confidence: 99%

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Homologous recombination in the archaeon Sulfolobus acidocaldarius: effects of DNA substrates and mechanistic implications

2013

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Although homologous recombination (HR) is known to influence the structure, stability, and evolution of microbial genomes, few of its functional properties have been measured in cells of hyperthermophilic archaea. The present study manipulated various properties of the parental DNAs in high-resolution assays of Sulfolobus acidocaldarius transformation, and measured the impact on the efficiency and pattern of marker transfer to the recipient chromosome. The relative orientation of homologous sequences, the type and position of chromosomal mutation being replaced, and the length of DNA flanking the marked region all affected the efficiency, linkage, tract continuity, and other parameters of marker transfer. Effects predicted specifically by the classical reciprocal-exchange model of HR were not observed. One analysis observed only 90 % linkage between markers defined by adjacent bases; in another series of experiments, sequence divergence up to 4 % had no detectable impact on overall efficiency of HR or on the co-transfer of a distal non-selected marker. The effects of introducing DNA via conjugation, rather than transformation, were more difficult to assess, but appeared to increase co-transfer (i.e. linkage) of relatively distant non-selected markers. The results indicate that HR events between gene-sized duplex DNAs and the S. acidocaldarius chromosome typically involve neither crossing over nor interference from a mismatch-activated anti-recombination system. Instead, the donor DNA may anneal to a transient chromosomal gap, as in the mechanism proposed for oligonucleotidemediated transformation of Sulfolobus and other micro-organisms.

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Section: Introductionmentioning

confidence: 85%

Section: J Rockwood and Othersmentioning

confidence: 99%

Section: Circularity and Orientation Of Donor Sequencesmentioning

confidence: 99%

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Homologous recombination in the archaeon Sulfolobus acidocaldarius: effects of DNA substrates and mechanistic implications

2013

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“…Without appropriate repair, DSBs may lead to cell lethality or cancer (2)(3)(4). Homologous recombination (HR) is a widely conserved essential mechanism for high-fidelity repair of DSBs (5)(6)(7)(8). HR is a highly coordinated multistep biochemical process, which is most elegantly demonstrated in the yeast Saccharomyces cerevisiae.…”

mentioning

confidence: 99%

PCNA is efficiently loaded on the DNA recombination intermediate to modulate polymerase δ, η, and ζ activities

Holzschu

Sugiyama

2013

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

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Proliferating cell nuclear antigen (PCNA) is required for DNA homologous recombination (HR), but its exact role is unclear. Here, we investigated the loading of PCNA onto a synthetic D-loop (DL) intermediate of HR and the functional interactions of PCNA with Rad51 recombinase and DNA polymerase (Pol) δ, Pol η, and Pol ζ. PCNA was loaded onto the synthetic DL as efficiently as it was loaded onto a primed DNA substrate. Efficient PCNA loading requires Replication Protein A, which is associated with the displaced ssDNA loop and provides a binding site for the clamp-loader Replication Factor C. Loaded PCNA greatly stimulates DNA synthesis by Pol δ within the DL but does not affect primer recognition by Pol δ. This suggests that the essential role of PCNA in HR is not recruitment of Pol δ to the DL but stimulation of Pol δ to displace a DNA strand during DL extension. Both Pol η and Pol ζ extended the DL more efficiently than Pol δ in the absence of PCNA, but little or no stimulation was observed in the presence of PCNA. Finally, Rad51 inhibited both the loading of PCNA onto the DL and the extension of the DL by Pol δ and Pol η. However, preloaded PCNA on the DL counteracts the Rad51-mediated inhibition of the DL extension. This suggests that the inhibition of postinvasion DNA synthesis by Rad51 occurs mostly at the step of PCNA loading.DNA repair | translesion polymerase | sliding clamp D NA double-strand breaks (DSBs) are introduced into the genome by several factors, including ionizing radiation, mutagenic chemicals, reactive oxygen species, and stalled DNA replication (1). Without appropriate repair, DSBs may lead to cell lethality or cancer (2-4). Homologous recombination (HR) is a widely conserved essential mechanism for high-fidelity repair of DSBs (5-8). HR is a highly coordinated multistep biochemical process, which is most elegantly demonstrated in the yeast Saccharomyces cerevisiae. Briefly, DSB ends are first processed by specialized exonucleases to generate 3′ overhangs (9-11), which are then coated with the ssDNA binding protein Replication Protein A (RPA). The Rad52 recombination mediator interacts with RPA and recruits Rad51 recombinase onto the ssDNA to form a helical nucleoprotein filament (12-15). This Rad51-ssDNA filament mediates strand invasion into a homologous dsDNA (16) to produce a DNA structure that is referred to as the D-loop (DL; see Fig. 6B). The 3′ end of the invading strand is used as the primer by DNA polymerases for DNA synthesis (postinvasion DNA synthesis), extending the DL (see Fig. 6F). After postinvasion DNA synthesis, repair may be completed by a break-induced replication, DSB repair, or synthesis-dependent strand-annealing pathway (5).Postinvasion DNA synthesis is crucial to high-fidelity repair of DSBs because it recovers the genetic information that might be lost during breakage events. Several DNA polymerases, including polymerase (Pol) δ, Pol η, and Pol ζ, are possibly involved in this process. Pol δ is known as a replicative polymerase that constitutes the replisome (17,...

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“…DNA synthesis from the 3' ends using the partner as a template and subsequent ligation form a double Holliday junction (dHJ). The pattern of resolution of this double-Holliday junction determines whether the recombination product is a crossover or a non-crossover [3][4][5]. The crossover corresponds to the chiasma, an important chromosome structure holding two homologs together from late prophase I to metaphase I-anaphase I transition.…”

Section: Genes Involved In Dsb Formation: Spo11 and Othersmentioning

confidence: 99%

Double-stranded DNA breaks and gene functions in recombination and meiosis

Mā

2006

Cell Res

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Gene functions in recombination and meiosis 402 npg REVIEW Meiotic prophase I is a long and complex phase. Homologous recombination is an important process that occurs between homologous chromosomes during meiotic prophase I. Formation of chiasmata, which hold homologous chromosomes together until the metaphase I to anaphase I transition, is critical for proper chromosome segregation. Recent studies have suggested that the SPO11 proteins have conserved functions in a number of organisms in generating sites of double-stranded DNA breaks (DSBs) that are thought to be the starting points of homologous recombination. Processing of these sites of DSBs requires the function of RecA homologs, such as RAD51, DMC1, and others, as suggested by mutant studies; thus the failure to repair these meiotic DSBs results in abnormal chromosomal alternations, leading to disrupted meiosis. Recent discoveries on the functions of these RecA homologs have improved the understanding of the mechanisms underlying meiotic homologous recombination.Cell Research (2006) Meiosis is a highly coordinated cell division, which generates four haploid reproductive cells required for sexual reproduction. Meiosis involves one round of DNA replication and two nuclear divisions, meiosis I and meiosis II. The first nuclear division leads to the segregation of homologous chromosomes (homologs), and is unique to meiosis. During the second division, sister chromatids are separated, resulting in the formation of four haploid nuclei and followed by the meiotic cytokinesis that forms four haploid cells. Similar to mitosis, both meiosis I and meiosis II can be divided into four stages: prophase, metaphase, anaphase, and telophase.However, meiosis I differs from meiosis II as meiosis I involves homology search, pairing, interhomolog recombination, and synapsis of homologs, processes that are required for correct association and segregation of homologs. The prophase stage of meiosis I, or prophase I, has been the target of interest because of the occurrence of these major processes of chromosome interactions. During early prophase I, arms of sister chromosomes are closely associated by protein complexes called cohesins, which are removed during the metaphase I/anaphase I transition. However, the centromere regions remained associated until the segregation of sister chromatids during meiosis II. Homologous pairing is the result of interaction between homologous chromosomes relying on the homology of DNA sequences [1,2], and is considered to be a transient and non-stable association between homologous chromosomes. Pairing between homologous chromosomes facilitates the process of recombination. The recombination process confers the interexchange of genetic information between non-sister chromatids, and generates chiasmata, which ensure proper association between homologous chromosomes prior to chromosome segregation at anaphase I. Synapsis, however, is a stable association by forming synaptonemal complexes between chromosomes. Synaptonemal complexes are threeparti...

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Repairing a double–strand chromosome break by homologous recombination: revisiting Robin Holliday's model

Cited by 69 publications

References 53 publications

Homologous recombination in the archaeon Sulfolobus acidocaldarius: effects of DNA substrates and mechanistic implications

Homologous recombination in the archaeon Sulfolobus acidocaldarius: effects of DNA substrates and mechanistic implications

PCNA is efficiently loaded on the DNA recombination intermediate to modulate polymerase δ, η, and ζ activities

Double-stranded DNA breaks and gene functions in recombination and meiosis

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