Mammalian CNTD1 is critical for meiotic crossover maturation and deselection of excess precrossover sites

Holloway, J. Kim; Sun, Xianfei; Yokoo, Rayka; Villeneuve, Anne M.; Cohen, Paula E.

doi:10.1083/jcb.201401122

Cited by 86 publications

(116 citation statements)

References 43 publications

(74 reference statements)

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“…Recent characterization of worm COSA-1 (crossover associated-1) and its mouse ortholog, CNTD1 (cyclin N-terminal domain-containing-1), have demonstrated an essential and conserved role in crossover formation (98, 231). These proteins have sequence similarity with cyclin B but also predict structural differences from the canonical cyclin family (231).…”

Section: Mechanisms Governing Crossoversmentioning

confidence: 99%

“…In C. elegans , COSA-1 functions to ensure crossover homeostasis when DSB levels are limiting and for the process of maturing DSBs to interhomolog crossovers (231). Both COSA-1 and CNTD1 mutants have meiotic defects that lead to a lack of crossovers, drastically reduced viability in worm, and infertility in mouse (98, 231). Specifically, cosa-1 mutants form normal DSBs and SC but fail to undergo SC remodeling consistent with crossover formation (231).…”

Section: Mechanisms Governing Crossoversmentioning

confidence: 99%

“…Specifically, cosa-1 mutants form normal DSBs and SC but fail to undergo SC remodeling consistent with crossover formation (231). In mouse, Cntd1 mutant males are defective in the transition from early pro-crossover factors MutSγ to the late pro-crossover MutLγ, leading to a prolonged persistence of MutSγ (98). In addition, RNF212 persists through pachynema, and HEI10 fails to load in Cntd1 mutant mice (98).…”

Section: Mechanisms Governing Crossoversmentioning

confidence: 99%

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Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

2016

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Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process of homologous recombination, whereby DNA double-strand breaks are introduced into the genome and are subsequently repaired to generate either noncrossovers or crossovers. Although homologous recombination is essential for chromosome pairing during prophase I, the resulting crossovers are critical for maintaining homolog interactions and enabling accurate segregation at the first meiotic division. Thus, the placement, timing, and frequency of crossover formation must be exquisitely controlled. In this review, we discuss the proteins involved in crossover formation, the process of their formation and designation, and the rules governing crossovers, all within the context of the important landmarks of prophase I. We draw together crossover designation data across organisms, analyze their evolutionary divergence, and propose a universal model for crossover regulation.

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Section: Mechanisms Governing Crossoversmentioning

confidence: 99%

Section: Mechanisms Governing Crossoversmentioning

confidence: 99%

Section: Mechanisms Governing Crossoversmentioning

confidence: 99%

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Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

2016

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“…A widely conserved solution for protecting potential CO intermediates involves the MutSg complex, comprising MSH4 and MSH5, meiosisspecific members of the MutS protein family that can form a sliding clamp on DNA in response to recognition of branched DNA structures (Baudat and De Massy 2007;Lynn et al 2007;Snowden et al 2004). In many organisms, MutSg is initially recruited to multiple sites in excess of eventual COs, but it becomes stabilized at only a subset of these sites through recruitment of other pro-CO factors (Kneitz et al 2000;Yokoo et al 2012;Reynolds et al 2013;Holloway et al 2014;Qiao et al 2014). The CO designation process is tightly regulated, yielding a highly nonrandom distribution in which a relatively small number of CO-based connections are formed between homologs, yet chromosome pairs lacking such connections are extremely rare.…”

mentioning

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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“…In addition to studying meiosis-specific proteins such as components of synaptonemal complex, those interacting with the SC, such as cohesins, multiprotein complexes that mediate cohesion, can be evaluated (reviewed in 10–12 ). Regulation of DNA crossover formation, processing, and maturation can be and have also been studied with this technique 13 . In addition, this technique has been performed following the use of methods to obtain specific populations of mouse spermatocytes: 1) following culture of spermatocytes in okadaic acid to induce progression to the G2/MI transition, yielding increased numbers of diplotene, diakinesis, and metaphase I spreads 14,15 and 2) after methods used to isolate an enriched population of pachytene spermatocytes 14 .…”

Section: Discussionmentioning

confidence: 99%

Preparation of Meiotic Chromosome Spreads from Mouse Spermatocytes

Dia

Strange

Liang

et al. 2017

JoVE

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SHORT ABSTRACT Meiosis is the developmental process by which gametes are formed through a single round of DNA replication and two successive rounds of chromosome segregation. Mammalian meiosis can be examined by utilizing a technique to prepare meiotic chromosome spreads. Here we demonstrate a method of preparing surface-spread nuclei from mouse spermatocytes. LONG ABSTRACT Mammalian meiosis is a dynamic developmental process that occurs in germ cells and can be studied and characterized. Using a method to spread nuclei on the surface of slides (rather than dropping them from a height), we demonstrate an optimized technique on mouse spermatocytes that was first described in 1997. This method is widely used in laboratories to study mammalian meiosis because it yields a plethora of high quality nuclei undergoing substages of prophase I. Seminiferous tubules are first placed in a hypotonic solution to swell spermatocytes. Then spermatocytes are released into a sucrose solution to create a cell suspension, and nuclei are spread onto fixative-soaked glass slides. Following immunostaining, a diversity of proteins germane to meiotic processes can be examined. For example, proteins of the synaptonemal complex, a tripartite structure that connects the chromosome axes/cores of homologs together can be easily visualized. Meiotic recombination proteins, which are involved in repair of DNA double-strand breaks by homologous recombination, can also be immunostained to evaluate progression of prophase I. Here we describe and demonstrate in detail a technique widely used to study mammalian meiosis in spermatocytes from juvenile or adult male mice.

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Mammalian CNTD1 is critical for meiotic crossover maturation and deselection of excess precrossover sites

Abstract: CNTD1 coordinates the maturation and designation of meiotic crossover sites from an excess pool of double-strand break intermediates by regulating dynamic changes in key protein complexes associated with these sites.

Cited by 86 publications

References 43 publications

Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

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

Preparation of Meiotic Chromosome Spreads from Mouse Spermatocytes

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