<scp>SYCP</scp>3 regulates strand invasion activities of <scp>RAD</scp>51 and <scp>DMC</scp>1

Kobayashi, Wataru; Hosoya, Noriko; Machida, Shuichi; Miyagawa, Kiyoshi; Kurumizaka, Hitoshi

doi:10.1111/gtc.12513

Cited by 19 publications

(12 citation statements)

References 59 publications

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“…Synaptonemal complex proteins like Scp1, Scp2 and Scp3 were found to be associated with TH2BS11ph mononucleosomes [59–65]. Synaptonemal complex proteins are implicated in proper crossover formation and completion of meiosis [66]. Trim28 is known to associate with Brdt to mediate transcriptional repression in spermatogenic cells [67].…”

Section: Resultsmentioning

confidence: 99%

TH2BS11ph histone mark is enriched in the unsynapsed axes of the XY body and predominantly associates with H3K4me3-containing genomic regions in mammalian spermatocytes

Mahadevan

Pentakota

Roy

et al. 2019

Epigenetics & Chromatin

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Background TH2B is a major histone variant that replaces about 80–85% of somatic H2B in mammalian spermatocytes and spermatids. The post-translational modifications (PTMs) on TH2B have been well characterised in spermatocytes and spermatids. However, the biological function(s) of these PTMs on TH2B have not been deciphered in great detail. In our attempt to decipher the unique function(s) of histone variant TH2B, we detected the modification in the N-terminal tail, Serine 11 phosphorylation on TH2B (TH2BS11ph) in spermatocytes. Results The current study is aimed at understanding the function of the TH2BS11ph modification in the context of processes that occur during meiotic prophase I. Immunofluorescence studies with the highly specific antibodies revealed that TH2BS11ph histone mark is enriched in the unsynapsed axes of the sex body and is associated with XY body-associated proteins like Scp3, γH2AX, pATM, ATR, etc. Genome-wide occupancy studies as determined by ChIP sequencing experiments in P20 C57BL6 mouse testicular cells revealed that TH2BS11ph is enriched in X and Y chromosomes confirming the immunofluorescence staining pattern in the pachytene spermatocytes. Apart from the localisation of this modification in the XY body, TH2BS11ph is majorly associated with H3K4me3-containing genomic regions like gene promoters, etc. These data were also found to corroborate with the ChIP sequencing data of TH2BS11ph histone mark carried out in P12 C57BL6 mouse testicular cells, wherein we found the predominant localisation of this modification at H3K4me3-containing genomic regions. Mass spectrometry analysis of proteins that associate with TH2BS11ph-containing mononucleosomes revealed key proteins linked with the functions of XY body, pericentric heterochromatin and transcription. Conclusions TH2BS11ph modification is densely localised in the unsynapsed axes of the XY body of the pachytene spermatocyte. By ChIP sequencing studies in mouse P12 and P20 testicular cells, we demonstrate that TH2BS11ph is predominantly associated with H3K4me3 positive genomic regions like gene promoters, etc. We propose that TH2BS11ph modification could act alone or in concert with other histone modifications to recruit the appropriate transcription or XY body recombination protein machinery at specific genomic loci.

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Section: Resultsmentioning

confidence: 99%

TH2BS11ph histone mark is enriched in the unsynapsed axes of the XY body and predominantly associates with H3K4me3-containing genomic regions in mammalian spermatocytes

Mahadevan

Pentakota

Roy

et al. 2019

Epigenetics & Chromatin

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“…Rad51 has a pivotal function in meiotic prophase in mice and its loss leads to depletion of late prophase I spermatocytes [39]. During meiosis, the two recombinases, Rad51 and Dmc1, interact with single-stranded DNA to form specialized filaments that are adapted for facilitating recombination between homologous chromosomes [40]. Both Rad51 and Dmc1 have an intrinsic ability to self-aggregate.…”

Section: Discussionmentioning

confidence: 99%

Global Transcriptome and Co-Expression Network Analysis Reveal Contrasting Response of Japonica and Indica Rice Cultivar to γ Radiation

Zhang

Huang

et al. 2019

IJMS

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Japonica and indica are two important subspecies in cultivated Asian rice. Irradiation is a classical approach to induce mutations and create novel germplasm. However, little is known about the differential response between japonica and indica rice after γ radiation. Here, we utilized the RNA sequencing and Weighted Gene Co-expression Network Analysis (WGCNA) to compare the transcriptome differences between japonica Nipponbare (NPB) and indica Yangdao6 (YD6) in response to irradiation. Japonica subspecies are more sensitive to irradiation than the indica subspecies. Indica showed a higher seedling survival rate than japonica. Irradiation caused more extensive DNA damage in shoots than in roots, and the severity was higher in NPB than in YD6. GO and KEGG pathway analyses indicate that the core genes related to DNA repair and replication and cell proliferation are similarly regulated between the varieties, however the universal stress responsive genes show contrasting differential response patterns in japonica and indica. WGCNA identifies 37 co-expressing gene modules and ten candidate hub genes for each module. This provides novel evidence indicating that certain peripheral pathways may dominate the molecular networks in irradiation survival and suggests more potential target genes in breeding for universal stress tolerance in rice.

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“…Given this, it is important to view GC tumour biology in the full light of the capabilities of these meiotic proteins (see below). SCYP3 produced outside the meiotic context has been shown to disrupt the activity of the tumour‐suppressing recombination regulator BRCA2 and can modulate the strand invasion capabilities of both the RAD51 and DMC1 (meiosis‐specific) recombinases that drive homologous recombination (Hosoya et al ., ; Kobayashi et al ., ) (Fig. ).…”

Section: Activation Of Meiotic Chromosome Regulators In Non‐germ Cellmentioning

confidence: 93%

“…Neither is SYCP3 expression suitable as meiotic entry marker without interrogating the functional activity of the SYCP3 protein, such as chromosomal association and further formation of the SC, or showing expression of genes in the associated meiotic gene cluster (Heaney et al ., ; Guo et al ., ). Aberrant, unscheduled SCYP3 expression outside the meiotic context has been shown in other cancers (Chung et al ., ; Cho et al ., 2014a; Kitano et al ., ), where it has the potential to disrupt the activity of BRCA2, potentially leading to the modulation of strand invasion capabilities for recombinases (RAD51 and DMC1), which in turn drive homologous recombination (Hosoya et al ., ; Kobayashi et al ., ) (see above). Moreover, GC tumour research has been mainly conducted in the mouse model and results should be cautiously translated into a human setting.…”

Section: Meiotic Factors In Testicular Germ Cell Tumours: Meiosis or mentioning

confidence: 94%

Meiotic gene activation in somatic and germ cell tumours

Feichtinger

McFarlane

2019

Andrology

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Background Germ cell tumours are uniquely associated with the gametogenic tissues of males and females. A feature of these cancers is that they can express genes that are normally tightly restricted to meiotic cells. This aberrant gene expression has been used as an indicator that these cancer cells are attempting a programmed germ line event, meiotic entry. However, work in non‐germ cell cancers has also indicated that meiotic genes can become aberrantly activated in a wide range of cancer types and indeed provide functions that serve as oncogenic drivers. Here, we review the activation of meiotic factors in cancers and explore commonalities between meiotic gene activation in germ cell and non‐germ cell cancers. Objectives The objectives of this review are to highlight key questions relating to meiotic gene activation in germ cell tumours and to offer possible interpretations as to the biological relevance in this unique cancer type. Materials and Methods PubMed and the GEPIA database were searched for papers in English and for cancer gene expression data, respectively. Results We provide a brief overview of meiotic progression, with a focus on the unique mechanisms of reductional chromosome segregation in meiosis I. We then offer detailed insight into the role of meiotic chromosome regulators in non‐germ cell cancers and extend this to provide an overview of how this might relate to germ cell tumours. Conclusions We propose that meiotic gene activation in germ cell tumours might not indicate an unscheduled attempt to enter a full meiotic programme. Rather, it might simply reflect either aberrant activation of a subset of meiotic genes, with little or no biological relevance, or aberrant activation of a subset of meiotic genes as positive tumour evolutionary/oncogenic drivers. These postulates provide the provocation for further studies in this emerging field.

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SYCP3 regulates strand invasion activities of RAD51 and DMC1

Cited by 19 publications

References 59 publications

TH2BS11ph histone mark is enriched in the unsynapsed axes of the XY body and predominantly associates with H3K4me3-containing genomic regions in mammalian spermatocytes

TH2BS11ph histone mark is enriched in the unsynapsed axes of the XY body and predominantly associates with H3K4me3-containing genomic regions in mammalian spermatocytes

Global Transcriptome and Co-Expression Network Analysis Reveal Contrasting Response of Japonica and Indica Rice Cultivar to γ Radiation

Meiotic gene activation in somatic and germ cell tumours

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