Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIα and RMI1

Bocquet, Nicolas; Bizard, Anna H.; Abdulrahman, Wassim; Larsen, Nicolai Balle; Faty, Mahamadou; Cavadini, Simone; Bunker, R.D.; Kowalczykowski, Stephen C.; Ćejka, Petr; Hickson, Ian D.; Thomä, Nicolas H.

doi:10.1038/nsmb.2775

Cited by 72 publications

(124 citation statements)

References 60 publications

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“…In isolation, Sgs1/ BLM can migrate HJs and unwind proteinfree D-loops (Karow et al 2000;van Brabant et al 2000;Bachrati et al 2006;Fasching et al 2015), but in combination with the single-strand passage activity of Top3 -Rmi1/TOPIIIa -RMI1 -RMI2, the STR/BTR complexes perform a unique re-action to dissociate dHJs into component duplexes. This convergent branch migration and decatenation reaction yields exclusively noncrossover products and has been termed dissolution to distinguish it from endonuclease-mediated resolution (Wu and Hickson 2003;Wu et al 2006;Bussen et al 2007;Singh et al 2008;Xu et al 2008;Bocquet et al 2014). Consistent with this activity, STR/BTR has potent anticrossover activity in vivo and is required for efficient homolog separation at meiosis I (Jessop et al 2006;Oh et al 2007;Chu and Hickson 2009;Bzymek et al 2010;Holloway et al 2010;Mankouri et al 2011;Seguela-Arnaud et al 2015).…”

Section: The Str/btr Ensembles Are Master Regulators Of Meiotic Jointmentioning

confidence: 90%

Meiotic Recombination: The Essence of Heredity

Hunter

2015

Cold Spring Harb Perspect Biol

694

869

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The study of homologous recombination has its historical roots in meiosis. In this context, recombination occurs as a programmed event that culminates in the formation of crossovers, which are essential for accurate chromosome segregation and create new combinations of parental alleles. Thus, meiotic recombination underlies both the independent assortment of parental chromosomes and genetic linkage. This review highlights the features of meiotic recombination that distinguish it from recombinational repair in somatic cells, and how the molecular processes of meiotic recombination are embedded and interdependent with the chromosome structures that characterize meiotic prophase. A more in-depth review presents our understanding of how crossover and noncrossover pathways of meiotic recombination are differentiated and regulated. The final section of this review summarizes the studies that have defined defective recombination as a leading cause of pregnancy loss and congenital disease in humans. MEIOSIS AND THE ROOTS OF RECOMBINATION RESEARCHT he concept of recombination emerged during the early 20th century, following the post-Mendel era of heredity research. Thomas Hunt Morgan's formal theory of gene linkage and crossing-over (Morgan 1913) was a synthesis of three key concepts: "the chromosome theory of inheritance," imparted by Wilhelm Roux, Walther Flemming, Theodor Boveri, and Walter Sutton; "gene linkage," an exception to Mendel's law of independent assortment, first reported by Carl Correns; and the "chiasmatype theory," derived from Frans Janssens' cytological observations of meiotic chromosomes. The first proof of the crossover theory came from Harriet Creighton and Barbara McClintock (Creighton and McClintock 1931), who were able to correlate cytological and genetic exchanges in maize.Experiments aimed at understanding the mechanism of meiotic recombination became dominated by fungal genetics because of the huge advantage afforded by being able to recover all four meiotic products. These elegant studies culminated in four key concepts that formed the foundation of molecular models of recombination: gene conversion, an exception to Mendel's principle of segregation, signaled a local nonreciprocal transfer of genetic information (Winkler 1930;Lindergren 1953;Mitchell 1955); postmeiotic segregation (PMS) indicated the presence of heteroduplex DNA (Olive 1959;Kitani et al. 1962) (Lissouba and Rizet 1960;Murray 1960); and the strong correlation between gene conversion/ PMS events and crossing-over led to the proposal that these processes were mechanistically linked (Kitani et al. 1962;Perkins 1962;Whitehouse 1963). MOLECULAR MODELS OF MEIOTIC RECOMBINATIONHolliday's classic model reconciled gene conversion, PMS, and crossing-over into a single mechanism with the key features of hybrid (heteroduplex) DNA formed via strand exchange, mismatch correction of hybrid DNA to yield gene conversion, and a four-way exchange junction that could be resolved to yield either crossover or noncrossover duplex products (Holliday...

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Section: The Str/btr Ensembles Are Master Regulators Of Meiotic Jointmentioning

confidence: 90%

Meiotic Recombination: The Essence of Heredity

Hunter

2015

Cold Spring Harb Perspect Biol

694

869

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“…The S. cerevisiae orthologous complex (STR, for Sgs1, Top3, and Rmi1) seems able to perform the same process in vivo (Dayani et al 2011). The crystal structure of human TOP3a + RMI1 shows that RMI1 provides an important function: the decatenation loop that modifies the opening and closing of TOP3a so it can promote dissolution rather than relaxation (Bocquet et al 2014). Drosophila BlmTOP3a can carry out the dissolution reaction in vitro (Plank et al 2006), but Rmi1 has been lost from Schizophora.…”

Section: Double-holliday Junction Modelmentioning

confidence: 99%

DNA Repair inDrosophila: Mutagens, Models, and Missing Genes

2017

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The numerous processes that damage DNA are counterbalanced by a complex network of repair pathways that, collectively, can mend diverse types of damage. Insights into these pathways have come from studies in many different organisms, including Drosophila melanogaster. Indeed, the first ideas about chromosome and gene repair grew out of Drosophila research on the properties of mutations produced by ionizing radiation and mustard gas. Numerous methods have been developed to take advantage of Drosophila genetic tools to elucidate repair processes in whole animals, organs, tissues, and cells. These studies have led to the discovery of key DNA repair pathways, including synthesis-dependent strand annealing, and DNA polymerase theta-mediated end joining. Drosophila appear to utilize other major repair pathways as well, such as base excision repair, nucleotide excision repair, mismatch repair, and interstrand crosslink repair. In a surprising number of cases, however, DNA repair genes whose products play important roles in these pathways in other organisms are missing from the Drosophila genome, raising interesting questions for continued investigations.

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“…Deletion mutants of all three proteins share similar resection defects in vivo , and Top3-Rmi1 also stimulates the 5 0 -resection capacity of Sgs1-Dna2 in vitro (Cejka et al 2010a;Niu et al 2010). A very recent crystal structure of the conserved core of the human TopIIIa-RMI1 complex illustrates how RMI1 might regulate TopIIIa through a long insertion loop that invades the central gate of the toroidal topoisomerase (Bocquet et al 2014). …”

Section: The Sgs1/blm-dna2 Resection Pathwaymentioning

confidence: 99%

Structural Studies of DNA End Detection and Resection in Homologous Recombination

Schiller

Seifert

Linke-Winnebeck

et al. 2014

Cold Spring Harbor Perspectives in Biology

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DNA double-strand breaks are repaired by two major pathways, homologous recombination or nonhomologous end joining. The commitment to one or the other pathway proceeds via different steps of resection of the DNA ends, which is controlled and executed by a set of DNA double-strand break sensors, endo-and exonucleases, helicases, and DNA damage response factors. The molecular choreography of the underlying protein machinery is beginning to emerge. In this review, we discuss the early steps of genetic recombination and double-strand break sensing with an emphasis on structural and molecular studies.

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Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIα and RMI1

Cited by 72 publications

References 60 publications

Meiotic Recombination: The Essence of Heredity

Meiotic Recombination: The Essence of Heredity

DNA Repair inDrosophila: Mutagens, Models, and Missing Genes

Structural Studies of DNA End Detection and Resection in Homologous Recombination

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