A Role for<i>Caenorhabditis elegans</i>Chromatin-Associated Protein HIM-17 in the Proliferation<i>vs</i>. Meiotic Entry Decision

Bessler, Jessica B.; Reddy, Kirthi C.; Hayashi, Michiko; Hodgkin, Jonathan; Villeneuve, Anne M.

doi:10.1534/genetics.107.070987

Cited by 29 publications

(27 citation statements)

References 40 publications

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“…Additional data suggest that DLC-1–DCH-1 may also promote meotic entry through an unknown partner of METT-10 (Dorsett and Schedl, 2009). We also note that unlike the situation in gld-1 mutants, germline tumors associated with mutations in mett-10 , him-17 , and teg-4 are not due to the de-differentiation of meiotic cells but result from prolonged maintenance of the mitotic state (Bessler et al, 2007; Dorsett and Schedl, 2009; Dorsett et al, 2009; Mantina et al, 2009). …”

Section: Germline Tumors: Intrinsic Mechanismsmentioning

confidence: 71%

“…Additional roles for epigenetic regulators of germline proliferation are inicated by findings that loss-of-function mutations in him-17 , which encodes a novel chromatin-associated protein, and mett-10 , an evolutionarily conserved putative histone methyltransferase, enhance germline over-proliferation in weak glp-1(gf) mutants (Reddy and Villeneuve, 2004; Bessler et al, 2007; Dorsett et al, 2009). In addition, certain alleles of mett-10 cause a partially penetrant tumorous phenotype on their own that can be suppressed by glp-1(lf) mutations (Dorsett et al, 2009).…”

Section: Germline Tumors: Intrinsic Mechanismsmentioning

confidence: 99%

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Cancer models in Caenorhabditis elegans

Kirienko

Mani

Fay

2010

Developmental Dynamics

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Although now dogma, the idea that non-vertebrate organisms such as yeast, worms, and flies could inform, and in some cases even revolutionize, our understanding of oncogenesis in humans was not immediately obvious. Aided by the conservative nature of evolution and the persistence of a cohort of devoted researchers, the role of model organisms as a key tool in solving the cancer problem has, however, become widely accepted. In this review, we focus on the nematode Caenorhabditis elegans and its diverse and sometimes surprising contributions to our understanding of the tumorigenic process. Specifically, we discuss findings in the worm that address a well-defined set of processes known to be deregulated in cancer cells including cell cycle progression, growth factor signaling, terminal differentiation, apoptosis, the maintenance of genome stability, and developmental mechanisms relevant to invasion and metastasis.

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Section: Germline Tumors: Intrinsic Mechanismsmentioning

confidence: 71%

Section: Germline Tumors: Intrinsic Mechanismsmentioning

confidence: 99%

Cancer models in Caenorhabditis elegans

Kirienko

Mani

Fay

2010

Developmental Dynamics

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“…Quantitative analyses of DAPI bodies in diakinesis oocytes: For Figure 4C and Figure 6, A and C, numbers of DNA bodies present in diakinesis oocytes (in the 23, 22, and 21 positions relative to the spermatheca) were assessed in intact adult hermaphrodites fixed in ethanol and stained with 49,6-diamidino-2-phenylindole (DAPI) as in Bessler et al (2007). Note that this analysis tends to overestimate the incidence of interhomolog connections, as sometimes univalents lie too close to each other to be resolved unambiguously.…”

Section: Cytological Analysesmentioning

confidence: 99%

DNA Helicase HIM-6/BLM Both Promotes MutSγ-Dependent Crossovers and Antagonizes MutSγ-Independent Interhomolog Associations During Caenorhabditis elegans Meiosis

et al. 2014

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Meiotic recombination is initiated by the programmed induction of double-strand DNA breaks (DSBs), lesions that pose a potential threat to the genome. A subset of the DSBs induced during meiotic prophase become designated to be repaired by a pathway that specifically yields interhomolog crossovers (COs), which mature into chiasmata that temporarily connect the homologs to ensure their proper segregation at meiosis I. The remaining DSBs must be repaired by other mechanisms to restore genomic integrity prior to the meiotic divisions. Here we show that HIM-6, the Caenorhabditis elegans ortholog of the RecQ family DNA helicase BLM, functions in both of these processes. We show that him-6 mutants are competent to load the MutSg complex at multiple potential CO sites, to generate intermediates that fulfill the requirements of monitoring mechanisms that enable meiotic progression, and to accomplish and robustly regulate CO designation. However, recombination events at a subset of CO-designated sites fail to mature into COs and chiasmata, indicating a pro-CO role for HIM-6/BLM that manifests itself late in the CO pathway. Moreover, we find that in addition to promoting COs, HIM-6 plays a role in eliminating and/or preventing the formation of persistent MutSg-independent associations between homologous chromosomes. We propose that HIM-6/BLM enforces biased outcomes of recombination events to ensure that both (a) CO-designated recombination intermediates are reliably resolved as COs and (b) other recombination intermediates reliably mature into noncrossovers in a timely manner.

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“…For Figure 8C, spe-9(hc88ts) and spe-9(hc88ts); htp-1 htp-2 L4 worms expressing GFPϻH2B and GFPϻtubulin were shifted from 20°C to 25°C for 17-20 h to inactivate sperm, resulting in a block to progression of oocyte meiosis (McNally and McNally 2005). In both cases, whole worms were fixed in ethanol (Bessler et al 2007) and stained with Hoechst 33258.…”

Section: Cytological Analysesmentioning

confidence: 99%

Crossovers trigger a remodeling of meiotic chromosome axis composition that is linked to two-step loss of sister chromatid cohesion

Martínez-Pérez¹,

Schvarzstein²,

Barroso³

et al. 2008

Genes Dev.

155

248

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Segregation of homologous chromosomes during meiosis depends on linkages (chiasmata) created by crossovers and on selective release of a subset of sister chromatid cohesion at anaphase I. DuringCaenorhabditis elegans meiosis, each chromosome pair forms a single crossover, and the position of this event determines which chromosomal regions will undergo cohesion release at anaphase I. Here we provide insight into the basis of this coupling by uncovering a large-scale regional change in chromosome axis composition that is triggered by crossovers. We show that axial element components HTP-1 and HTP-2 are removed during late pachytene, in a crossover-dependent manner, from the regions that will later be targeted for anaphase I cohesion release. We demonstrate correspondence in position and number between chiasmata and HTP-1/2-depleted regions and provide evidence that HTP-1/2 depletion boundaries mark crossover sites. In htp-1 mutants, diakinesis bivalents lack normal asymmetrical features, and sister chromatid cohesion is prematurely lost during the meiotic divisions. We conclude that HTP-1 is central to the mechanism linking crossovers with late-prophase bivalent differentiation and defines the domains where cohesion will be protected until meiosis II. Further, we discuss parallels between the pattern of HTP-1/2 removal in response to crossovers and the phenomenon of crossover interference.[Keywords: Meiosis; chromosome axes; crossover; sister chromatid cohesion; chromosome remodeling; crossover interference] Supplemental material is available at http://www.genesdev.org. Received May 12, 2008; revised version accepted August 18, 2008. In sexually reproducing organisms, diploid germ cells produce haploid gametes through the specialized cell division program of meiosis. At the onset of meiosis, DNA is replicated and sister chromatid cohesion (SCC) is established (Nasmyth and Schleiffer 2004). In contrast to mitotic cell cycles, this single round of meiotic DNA replication is followed by two rounds of cell division, the first segregating homologous chromosomes (homologs), and the second segregating sister chromatids (Petronczki et al. 2003). This pattern of segregation requires an extended prophase during which chromosomes must assemble meiosis-specific axial structures, locate, and align with their homologs, stabilize this alignment through assembly of the synaptonemal complex (SC), and undergo crossover recombination events between their DNA molecules (Page and Hawley 2003). Crossovers that form in this context play a crucial role in promoting meiotic chromosome segregation, as they collaborate with SCC (on domains flanking the crossover site) to form the basis of chiasmata, cytologically visible connections between the homologs that are revealed upon SC disassembly and structural remodeling of chromosomes during late prophase (Jones 1987). Chiasmata allow homologs to remain connected while orienting away from each other toward opposite poles of the metaphase I spindle. Subsequently, the SCC that maintains the co...

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A Role forCaenorhabditis elegansChromatin-Associated Protein HIM-17 in the Proliferationvs. Meiotic Entry Decision

Cited by 29 publications

References 40 publications

Cancer models in Caenorhabditis elegans

Cancer models in Caenorhabditis elegans

DNA Helicase HIM-6/BLM Both Promotes MutSγ-Dependent Crossovers and Antagonizes MutSγ-Independent Interhomolog Associations During Caenorhabditis elegans Meiosis

Crossovers trigger a remodeling of meiotic chromosome axis composition that is linked to two-step loss of sister chromatid cohesion

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