Cohesin SMC1β protects telomeres in meiocytes

Adelfalk, Caroline; Janschek, Johannes; Revenkova, Ekaterina; Blei, Cornelia; Liebe, Bodo; Göb, Eva; Alsheimer, Manfred; Benavente, Ricardo; Boer, Esther de; Novak, Ivana; Höög, Christer; Scherthan, Harry; Jessberger, Rolf

doi:10.1083/jcb.200808016

Cited by 83 publications

(134 citation statements)

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“…Thus, we speculate that at least two non-mutually exclusive events might lead to the appearance of internal telomeres in the absence of CDK2. The first one implies that some telomeres are unable to attach to the nuclear envelope during leptotene, and therefore remain in the nucleoplasm in further prophase I stages, as described in knockout mouse models for Smc1b 2/2 and Sun1 2/2 mice (Adelfalk et al, 2009;Ding et al, 2007). An alternative, and more fascinating possibility, consists in the detachment of telomeres that were initially attached to the nuclear envelope, accounting for the increase in the rate of non-attached telomeres in zygotene and pachytene-like nuclei.…”

Section: Cdk2 Mediates Meiotic Telomere Attachment and Dynamicsmentioning

confidence: 99%

“…Indeed, the fact that the number of internal SUN1 foci increased during prophase I progression, as synapsis proceeds, also reinforces this proposal. In this context, it has been shown that SUN1 persists at the axial and lateral elements ends on spread spermatocytes after a harsh preparative technique that disrupts the nuclear envelope (Adelfalk et al, 2009;Ding et al, 2007;Morimoto et al, 2012). Accordingly, SUN1 at detached telomeres in Cdk2 2/2 spermatocytes could bring with them vesicles derived from the nuclear envelope.…”

Section: Cdk2 Mediates Meiotic Telomere Attachment and Dynamicsmentioning

confidence: 99%

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CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase

Viera

Alsheimer

Gómez

et al. 2014

Journal of Cell Science

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In most organisms, telomeres attach to the nuclear envelope at the onset of meiosis to promote the crucial processes of pairing, recombination and synapsis during prophase I. This attachment of meiotic telomeres is mediated by the specific distribution of several nuclear envelope components that interact with the attachment plates of the synaptonemal complex. We have determined by immunofluorescence and electron microscopy that the ablation of the kinase CDK2 alters the nuclear envelope in mouse spermatocytes, and that the proteins SUN1, KASH5 (also known as CCDC155) and lamin C2 show an abnormal cap-like distribution facing the centrosome. Strikingly, some telomeres are not attached to the nuclear envelope but remain at the nuclear interior where they are associated with SUN1 and with nuclear-envelope-detached vesicles. We also demonstrate that mouse testis CDK2 phosphorylates SUN1 in vitro. We propose that during mammalian prophase I the kinase CDK2 is a key factor governing the structure of the nuclear envelope and the telomere-led chromosome movements essential for homolog pairing.

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Section: Cdk2 Mediates Meiotic Telomere Attachment and Dynamicsmentioning

confidence: 99%

Section: Cdk2 Mediates Meiotic Telomere Attachment and Dynamicsmentioning

confidence: 99%

CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase

Viera

Alsheimer

Gómez

et al. 2014

Journal of Cell Science

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“…The absence of this protein leads to defects in chromosome synapsis, recombination, and meiotic progression in mammals (Ding et al 2007;Link et al 2014). We investigated the location of SUN1 protein using an antibody against mouse SUN1 (Adelfalk et al 2009). We found that SUN1 localized at the telomeres of meiotic bivalents in the Mongolian gerbil ( Figure 7A) as a single or double spot at the end of the SC.…”

Section: Association Of Centromeric Regions With the Nuclear Envelopementioning

confidence: 99%

Chromatin Organization and Remodeling of Interstitial Telomeric Sites During Meiosis in the Mongolian Gerbil (Meriones unguiculatus)

et al. 2014

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Telomeric DNA repeats are key features of chromosomes that allow the maintenance of integrity and stability in the telomeres. However, interstitial telomere sites (ITSs) can also be found along the chromosomes, especially near the centromere, where they may appear following chromosomal rearrangements like Robertsonian translocations. There is no defined role for ITSs, but they are linked to DNA damage-prone sites. We were interested in studying the structural organization of ITSs during meiosis, a kind of cell division in which programmed DNA damage events and noticeable chromatin reorganizations occur. Here we describe the presence of highly amplified ITSs in the pericentromeric region of Mongolian gerbil (Meriones unguiculatus) chromosomes. During meiosis, ITSs show a different chromatin conformation than DNA repeats at telomeres, appearing more extended and accumulating heterochromatin markers. Interestingly, ITSs also recruit the telomeric proteins RAP1 and TRF1, but in a stage-dependent manner, appearing mainly at late prophase I stages. We did not find a specific accumulation of DNA repair factors to the ITSs, such as gH2AX or RAD51 at these stages, but we could detect the presence of MLH1, a marker for reciprocal recombination. However, contrary to previous reports, we did not find a specific accumulation of crossovers at ITSs. Intriguingly, some centromeric regions of metacentric chromosomes may bind the nuclear envelope through the association to SUN1 protein, a feature usually performed by telomeres. Therefore, ITSs present a particular and dynamic chromatin configuration in meiosis, which could be involved in maintaining their genetic stability, but they additionally retain some features of distal telomeres, provided by their capability to associate to telomere-binding proteins.

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“…The identity of each population was confirmed by assessing the type of SCP3 immunofluorescence on chromosomes of sorted cells from each subset. To confirm that cell populations, which by Hoechst staining appeared as 4N are indeed spermatocytes, we crossed the Rad9a f/del Cre + line to transgenic mice expressing EGFP under the meiosis-specific Smc1b promoter described previously (Adelfalk et al, 2009). In this mouse line EGFP expression starts at the onset of prophase I.…”

Section: Immunofluorescencementioning

confidence: 99%

The DNA damage checkpoint protein RAD9A is essential for male meiosis in the mouse

Vasil’eva

Hopkins

Wang

et al. 2013

Journal of Cell Science

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SummaryIn mitotic cells, RAD9A functions in repairing DNA double-strand breaks (DSBs) by homologous recombination and facilitates the process by cell cycle checkpoint control in response to DNA damage. DSBs occur naturally in the germline during meiosis but whether RAD9A participates in repairing such breaks is not known. In this study, we determined that RAD9A is indeed expressed in the male germ line with a peak of expression in late pachytene and diplotene stages, and the protein was found associated with the XY body. As complete loss of RAD9A is embryonic lethal, we constructed and characterized a mouse strain with Stra8-Cre driven germ cell-specific ablation of Rad9a beginning in undifferentiated spermatogonia in order to assess its role in spermatogenesis. Adult mutant male mice were infertile or sub-fertile due to massive loss of spermatogenic cells. The onset of this loss occurs during meiotic prophase, and there was an increase in the numbers of apoptotic spermatocytes as determined by TUNEL. Spermatocytes lacking RAD9A usually arrested in meiotic prophase, specifically in pachytene. The incidence of unrepaired DNA breaks increased, as detected by accumulation of cH2AX and DMC1 foci on the axes of autosomal chromosomes in pachytene spermatocytes. The DNA topoisomerase IIb-binding protein 1 (TOPBP1) was still localized to the sex body, albeit with lower intensity, suggesting that RAD9A may be dispensable for sex body formation. We therefore show for the first time that RAD9A is essential for male fertility and for repair of DNA DSBs during meiotic prophase I.

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Cohesin SMC1β protects telomeres in meiocytes

Abstract: Telomeres fail to attach to the nuclear envelope and lose structural integrity in cells lacking SMC1β.

Cited by 83 publications

References 50 publications

CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase

CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase

Chromatin Organization and Remodeling of Interstitial Telomeric Sites During Meiosis in the Mongolian Gerbil (Meriones unguiculatus)

The DNA damage checkpoint protein RAD9A is essential for male meiosis in the mouse

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