RecQ Helicase, Sgs1, and XPF Family Endonuclease, Mus81-Mms4, Resolve Aberrant Joint Molecules during Meiotic Recombination

Oh, Steve D.; Lao, Jessica P.; Taylor, Andrew F.; Smith, Gerald R.; Hunter, Neil

doi:10.1016/j.molcel.2008.07.006

Cited by 159 publications

(230 citation statements)

References 55 publications

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“…Possibly, the comparatively higher frequency of MLH1-negative RNs in heterochromatin is related to the high frequency of repetitive sequences (32). Such sequences may be more likely to form unusual and complex recombination intermediates that can be resolved as COs by the MUS81-dependent CO pathway (6,29,34,35). At a more applied level, modifying local recombination frequencies in pericentric regions is an important challenge for plant breeding (e.g., for positional cloning), and knowing that heterochromatic regions are more prone to class II COs may lead to new strategies to promote COs in those regions, e.g., by mutating the FANCM gene that has been shown to specifically suppress class II COs in Arabidopsis (14).…”

Section: Resultsmentioning

confidence: 99%

“…Interference from early class I COs would lead to a higher proportion of class II COs occurring away from the initiation regions (see below for evidence of interaction between the two pathways). Furthermore, any recombination intermediates that form among the repetitive sequences in pericentric heterochromatin may be more likely to have aberrant structures that require MUS81 for resolution (34), leading to a comparatively high frequency of MLH1-negative RNs in heterochromatin.…”

Section: Resultsmentioning

confidence: 99%

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Combined fluorescent and electron microscopic imaging unveils the specific properties of two classes of meiotic crossovers

Anderson

Lohmiller

Tang

et al. 2014

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

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Crossovers (COs) shuffle genetic information and allow balanced segregation of homologous chromosomes during the first division of meiosis. In several organisms, mutants demonstrate that two molecularly distinct pathways produce COs. One pathway produces class I COs that exhibit interference (lowered probability of nearby COs), and the other pathway produces class II COs with little or no interference. However, the relative contributions, genomic distributions, and interactions of these two pathways are essentially unknown in nonmutant organisms because marker segregation only indicates that a CO has occurred, not its class type. Here, we combine the efficiency of light microscopy for revealing cellular functions using fluorescent probes with the high resolution of electron microscopy to localize and characterize COs in the same sample of meiotic pachytene chromosomes from wild-type tomato. To our knowledge, for the first time, every CO along each chromosome can be identified by class to unveil specific characteristics of each pathway. We find that class I and II COs have different recombination profiles along chromosomes. In particular, class II COs, which represent about 18% of all COs, exhibit no interference and are disproportionately represented in pericentric heterochromatin, a feature potentially exploitable in plant breeding. Finally, our results demonstrate that the two pathways are not independent because there is interference between class I and II COs.E ukaryotic sexual reproduction involves meiosis, a specialized cell division in which DNA duplication in a diploid cell is followed by two cell divisions to produce four haploid cells. The first division, Meiosis I, involves crossing over and chiasmata formation between each pair of homologous chromosomes, thereby ensuring separation of the homologs and formation of two haploid cells, each with one complete set of replicated chromosomes. The second division, Meiosis II, is a mitosis-like division in which the two sister chromatids separate to yield four haploid cells that directly or indirectly form gametes. Because these four products are genetically unique due to crossing over and independent segregation of homologous chromosomes during Meiosis I, meiosis plays an important role in creating genetic diversity in sexually reproducing organisms.Crossing over during meiosis is tightly controlled so each pair of homologs has at least one "obligate" crossover (CO) that ensures balanced reductional segregation, but the presence of a CO reduces the likelihood of another CO in its vicinity, a phenomenon referred to as CO interference (1, 2). Significant progress has been made recently in illuminating the molecular events of meiotic recombination and the control of crossing over (3)(4)(5)(6)(7)(8). The initiating event of meiotic recombination in most organisms is formation of numerous DNA double-strand breaks (DSBs). Homolog-dependent repair of a DSB may follow any one of at least three pathways: (i) non-CO that may result in a short gene conversion; (ii) CO ...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Combined fluorescent and electron microscopic imaging unveils the specific properties of two classes of meiotic crossovers

Anderson

Lohmiller

Tang

et al. 2014

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

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“…These two phenotypes are similar to the meiotic depletion alleles of top3/rmi1 that disrupt decatenase activity and lead to the accumulation of unresolved JMs. These mutations block nuclear divisions without disrupting the meiotic program, also known as "meiotic catastrophe" (Gangloff et al 1999;Jessop and Lichten 2008;Oh et al 2008;Kaur et al 2015;Tang et al 2015). Similar to the top3/rmi1 mutants, deletion of SPO11 or mutating the catalytic residue of SPO11 (SPO11-Y135F) suppressed the nup2D ndj1D block to nuclear divisions, presumably by eliminating a physical constraint caused by intermediates, or aberrant structures, associated with meiotic recombination.…”

Section: Discussionmentioning

confidence: 99%

The Nucleoporin Nup2 Contains a Meiotic-Autonomous Region that Promotes the Dynamic Chromosome Events of Meiosis

Chu

Gromova²,

Newman³

et al. 2017

Genetics

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Meiosis is a specialized cellular program required to create haploid gametes from diploid parent cells. Homologous chromosomes pair, synapse, and recombine in a dynamic environment that accommodates gross chromosome reorganization and significant chromosome motion, which are critical for normal chromosome segregation. In Saccharomyces cerevisiae, Ndj1 is a meiotic telomere-associated protein required for physically attaching telomeres to proteins embedded in the nuclear envelope. In this study, we identified additional proteins that act at the nuclear periphery from meiotic cell extracts, including Nup2, a nonessential nucleoporin with a known role in tethering interstitial chromosomal loci to the nuclear pore complex. We found that deleting NUP2 affects meiotic progression and spore viability, and gives increased levels of recombination intermediates and products. We identified a previously uncharacterized 125 aa region of Nup2 that is necessary and sufficient for its meiotic function, thus behaving as a meiotic autonomous region (MAR). Nup2-MAR forms distinct foci on spread meiotic chromosomes, with a subset overlapping with Ndj1 foci. Localization of Nup2-MAR to meiotic chromosomes does not require Ndj1, nor does Ndj1 localization require Nup2, suggesting these proteins function in different pathways, and their interaction is weak or indirect. Instead, several severe synthetic phenotypes are associated with the nup2D ndj1D double mutant, including delayed turnover of recombination joint molecules, and a failure to undergo nuclear divisions without also arresting the meiotic program. These data suggest Nup2 and Ndj1 support partially overlapping functions that promote two different levels of meiotic chromosome organization necessary to withstand a dynamic stage of the eukaryotic life cycle.

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“…In yeast mitotic cells, we and others demonstrated that two DNA helicases, Sgs1 and Srs2, suppress crossovers in DSBinduced and spontaneous recombination, but in different ways (Ira et al 2003;Lo et al 2006;Robert et al 2006). Sgs1 was also shown to suppress crossing over in the meiotic cycle, particularly when three or four chromatids are involved in recombination (Jessop et al 2006;Oh et al 2007Oh et al , 2008Jessop and Lichten 2008). Srs2 appears to promote steps in the SDSA pathway, whereas Sgs1 and its associated topoisomerase Top3 reduce crossovers apparently by resolving the dHJ in a noncrossover manner.…”

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confidence: 91%

Yeast Mph1 helicase dissociates Rad51-made D-loops: implications for crossover control in mitotic recombination

Prakash¹,

Satory²,

Dray³

et al. 2009

Genes Dev.

231

342

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Eukaryotes possess mechanisms to limit crossing over during mitotic homologous recombination, thus avoiding possible chromosomal rearrangements. We show here that budding yeast Mph1, an ortholog of human FancM helicase, utilizes its helicase activity to suppress spontaneous unequal sister chromatid exchanges and DNA double-strand break-induced chromosome crossovers. Since the efficiency and kinetics of break repair are unaffected, Mph1 appears to channel repair intermediates into a noncrossover pathway. Importantly, Mph1 works independently of two other helicases-Srs2 and Sgs1-that also attenuate crossing over. By chromatin immunoprecipitation, we find targeting of Mph1 to double-strand breaks in cells. Purified Mph1 binds D-loop structures and is particularly adept at unwinding these structures. Importantly, Mph1, but not a helicase-defective variant, dissociates Rad51-made D-loops. Overall, the results from our analyses suggest a new role of Mph1 in promoting the noncrossover repair of DNA double-strand breaks.[Keywords: Genome instability; recombination; DNA helicase; crossing over; Fanconi anemia] Supplemental material is available at http://www.genesdev.org. Received September 8, 2008; revised version accepted November 12, 2008. DNA double-strand breaks (DSBs) that arise during DNA replication or are induced by DNA damaging agents, such as ionizing radiation, are frequently repaired by homologous recombination (HR). In yeast and other eukaryotes, the RAD52 epistasis group of proteins mediate homologous recombination (for reviews, see Paques and Haber 1999;Krogh and Symington 2004). In this process, DSB ends are resected by nucleases to create 39 ssDNA that becomes coated with the recombinase protein Rad51. The Rad51-ssDNA nucleoprotein filament then carries out a search for a homologous donor DNA sequence and promotes strand invasion of the donor molecule to form a D-loop (Sung and Klein 2006). After D-loop formation, there appear to be two alternative pathways that result in DSB repair. One pathway involves the formation of a double Holliday junction (dHJ) that can be resolved by symmetrical strand cleavage into either a crossover or noncrossover gene conversion (Szostak et al. 1983). An alternative mechanism, called synthesis-dependent strand annealing (SDSA), posits formation mostly of noncrossovers, and in most cases does not involve a dHJ intermediate (for review, see Paques and Haber 1999). In support of the SDSA model of gene conversion, we showed recently that both newly synthesized strands are inherited by the broken recipient DNA molecule (Ira et al. 2006). The choice between crossover and noncrossover is tightly regulated in both mitotic and meiotic cells. In meiotic S. cerevisiae cells the correct number of crossovers are required for proper chromosome segregation; the proportion of gene conversion accompanied by crossing over varies between 25% and 50% depending on the locus (Roeder 1995). In mitotic cells, the proportion of crossovers is much lower, ranging between <1% and 7 These authors c...

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RecQ Helicase, Sgs1, and XPF Family Endonuclease, Mus81-Mms4, Resolve Aberrant Joint Molecules during Meiotic Recombination

Cited by 159 publications

References 55 publications

Combined fluorescent and electron microscopic imaging unveils the specific properties of two classes of meiotic crossovers

Combined fluorescent and electron microscopic imaging unveils the specific properties of two classes of meiotic crossovers

The Nucleoporin Nup2 Contains a Meiotic-Autonomous Region that Promotes the Dynamic Chromosome Events of Meiosis

Yeast Mph1 helicase dissociates Rad51-made D-loops: implications for crossover control in mitotic recombination

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