AIMS: Embryonal tumours with PLAGL1 or PLAGL2 amplification (ET, PLAGL) show substantial heterogeneity regarding their clinical characteristics and have been treated inconsistently, resulting in diverse outcomes. In this study, we aimed to evaluate the clinical behaviour of ET, PLAGL and elucidate their response pattern across the different applied treatment regimens. METHODS: We conducted an in-depth retrospective analysis of clinical and serial imaging data of 18 patients with ET, PLAGL (nine each of PLAGL1 and PLAGL2 amplified). RESULTS: Patients with PLAGL1-amplified tumours (ET, PLAGL1) had fewer relapses (3/9), while PLAGL2-amplified tumours (ET, PLAGL2) were prone to early relapse or progression (8/9) and to distant, leptomeningeal and intraventricular relapses. Progression-free survival differed significantly between the subtypes (log-rank test, p = 0.0055). Postoperative treatment included chemotherapy (n = 17, various protocols), alone (n = 8) or combined with radiotherapy (n = 9). Responses to chemotherapy were observed in both subtypes, and incomplete resection was not associated with inferior survival. All three survivors with ET, PLAGL2 were treated with induction and high-dose chemotherapy with (n = 1-low-dose CSI and boost) or without (n = 2) radiotherapy, whereas five patients with less intensive chemotherapy relapsed. All six survivors with ET, PLAGL1 were treated with conventional chemotherapy regimens, with (n = 4-local radiotherapy n = 3; CSI and boost n = 1) or without (n = 2) radiotherapy. Two patients with ET, PLAGL1 relapsed after 8 years. CONCLUSIONS: Adjuvant therapy should be considered for all ET, PLAGL patients: Patients with ET, PLAGL2 might benefit from intensified chemotherapy regimens. In contrast, patients with ET, PLAGL1 showed superior outcomes without high-dose chemotherapy or craniospinal irradiation.
- Klíčová slova
- PLAGL1, PLAGL2, ET, PLAGL, embryonal CNS tumour, treatment,
- MeSH
- amplifikace genu MeSH
- dítě MeSH
- DNA vazebné proteiny * genetika MeSH
- dospělí MeSH
- germinální a embryonální nádory * genetika terapie patologie diagnostické zobrazování MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory centrálního nervového systému * genetika terapie patologie diagnostické zobrazování MeSH
- nádory mozku * genetika terapie MeSH
- předškolní dítě MeSH
- retrospektivní studie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- DNA vazebné proteiny * MeSH
Methylation of histone H3 at lysine 36 (H3K36me3) marks active chromatin. The mark is interpreted by epigenetic readers that assist transcription and safeguard chromatin fiber integrity. In Drosophila, the chromodomain protein MSL3 binds H3K36me3 at X-chromosomal genes to implement dosage compensation. The PWWP-domain protein JASPer recruits the JIL1 kinase to active chromatin on all chromosomes. Because depletion of K36me3 had variable, locus-specific effects on the interactions of those readers, we systematically studied K36 methylation in a defined cellular model. Contrasting prevailing models, we found that K36me1, K36me2, and K36me3 each contribute to distinct chromatin states. Monitoring the changing K36 methylation landscape upon depletion of the three methyltransferases Set2, NSD, and Ash1 revealed local, context-specific methylation signatures. Each methyltransferase governs K36 methylation in dedicated genomic regions, with minor overlaps. Set2 catalyzes K36me3 predominantly at transcriptionally active euchromatin. NSD places K36me2/3 at defined loci within pericentric heterochromatin and on weakly transcribed euchromatic genes. Ash1 deposits K36me1 at putative enhancers. The mapping of MSL3 and JASPer suggested that they bind K36me2 in addition to K36me3, which was confirmed by direct affinity measurement. This dual specificity attracts the readers to a broader range of chromosomal locations and increases the robustness of their actions.
- MeSH
- chromatin * metabolismus MeSH
- DNA vazebné proteiny metabolismus genetika MeSH
- Drosophila melanogaster genetika metabolismus MeSH
- euchromatin metabolismus genetika MeSH
- heterochromatin metabolismus genetika MeSH
- histonlysin-N-methyltransferasa * metabolismus genetika MeSH
- histony * metabolismus MeSH
- lysin metabolismus MeSH
- metylace MeSH
- protein-serin-threoninkinasy MeSH
- proteiny Drosophily * metabolismus genetika MeSH
- transkripční faktory metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ASH1 protein, Drosophila MeSH Prohlížeč
- chromatin * MeSH
- DNA vazebné proteiny MeSH
- euchromatin MeSH
- heterochromatin MeSH
- histonlysin-N-methyltransferasa * MeSH
- histony * MeSH
- JIL-1 protein, Drosophila MeSH Prohlížeč
- lysin MeSH
- protein-serin-threoninkinasy MeSH
- proteiny Drosophily * MeSH
- transkripční faktory MeSH
BACKGROUND AND PURPOSE: CNS embryonal tumor with pleomorphic adenoma gene-like 1 (PLAGL1)/pleomorphic adenoma gene-like 2 (PLAGL2) amplification (ET, PLAGL) is a newly identified, highly malignant pediatric tumor. Systematic MRI descriptions of ET, PLAGL are currently lacking. MATERIALS AND METHODS: MRI data from 19 treatment-naïve patients with confirmed ET, PLAGL were analyzed. Evaluation focused on anatomic involvement, tumor localization, MRI signal characteristics, DWI behavior, and the presence of necrosis and hemorrhage. Descriptive statistics (median, interquartile range, percentage) were assessed. RESULTS: Ten patients had PLAGL1 and nine had PLAGL2 amplifications. The solid components of the tumors were often multinodular with heterogeneous enhancement (mild to intermediate in 47% and intermediate to strong in 47% of cases). Nonsolid components included cysts in 47% and necrosis in 84% of the cases. The tumors showed heterogeneous T2WI hyper- and isointensity (74%), relatively little diffusion restriction (ADC values less than contralateral normal-appearing WM in 36% of cases with available DWI), and tendencies toward hemorrhage/calcification (42%). No reliable distinction was found between PLAGL1- and PLAGL2-amplified tumors or compared with other embryonal CNS tumors. CONCLUSIONS: The study contributes to understanding the imaging characteristics of ET, PLAGL. It underscores the need for collaboration in studying rare pediatric tumors and advocates the use of harmonized imaging protocols for better characterization.
- MeSH
- amplifikace genu MeSH
- dítě MeSH
- DNA vazebné proteiny * genetika MeSH
- gen SMARCB1 MeSH
- germinální a embryonální nádory * genetika patologie MeSH
- kojenec MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- mladiství MeSH
- nádory mozku * genetika patologie MeSH
- předškolní dítě MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- transkripční faktory * genetika MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA vazebné proteiny * MeSH
- gen SMARCB1 MeSH
- PLAG1 protein, human MeSH Prohlížeč
- SMARCB1 protein, human MeSH Prohlížeč
- transkripční faktory * MeSH
Replication stress, particularly in hard-to-replicate regions such as telomeres and centromeres, leads to the accumulation of replication intermediates that must be processed to ensure proper chromosome segregation. In this study, we identify a critical role for the interaction between RECQ4 and MUS81 in managing such stress. We show that RECQ4 physically interacts with MUS81, targeting it to specific DNA substrates and enhancing its endonuclease activity. Loss of this interaction, results in significant chromosomal segregation defects, including the accumulation of micronuclei, anaphase bridges, and ultrafine bridges (UFBs). Our data further demonstrate that the RECQ4-MUS81 interaction plays an important role in ALT-positive cells, where MUS81 foci primarily colocalise with telomeres, highlighting its role in telomere maintenance. We also observe that a mutation associated with Rothmund-Thomson syndrome, which produces a truncated RECQ4 unable to interact with MUS81, recapitulates these chromosome instability phenotypes. This underscores the importance of RECQ4-MUS81 in safeguarding genome integrity and suggests potential implications for human disease. Our findings demonstrate the RECQ4-MUS81 interaction as a key mechanism in alleviating replication stress at hard-to-replicate regions and highlight its relevance in pathological conditions such as RTS.
- MeSH
- chromozomální nestabilita MeSH
- DNA vazebné proteiny * metabolismus genetika MeSH
- endonukleasy * metabolismus genetika MeSH
- helikasy RecQ * metabolismus genetika MeSH
- homeostáza telomer MeSH
- lidé MeSH
- mutace MeSH
- replikace DNA * MeSH
- Rothmundův-Thomsonův syndrom * genetika metabolismus MeSH
- segregace chromozomů MeSH
- telomery * metabolismus genetika MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA vazebné proteiny * MeSH
- endonukleasy * MeSH
- helikasy RecQ * MeSH
- MUS81 protein, human MeSH Prohlížeč
- RECQL4 protein, human MeSH Prohlížeč
Myoepithelial neoplasms of the skin and soft tissue still represent a confusing and somewhat controversial field in pathology as it appears that this category includes several different entities. However, recent studies have suggested that both apocrine mixed tumors (AMT) and cutaneous myoepitheliomas (CM) harbor identical chromosomal rearrangements involving the PLAG1 gene and hence may represent a morphological spectrum. The aim of the present study was to share our institutional experience with these tumors and specifically focus on studying their immunohistochemical and molecular features to further assess their relatedness. Eleven cases of AMT and 7 cases of CM were collected and analyzed using immunohistochemistry (IHC), PLAG1 FISH, and Archer FusionPlex assay. There were 14 male and 4 female patients with ages ranging from 26 to 85 years (median 55.8 years, mean 58.5 years). AMTs were mainly located in the head and neck (n = 10), while CMs were mainly located in the acral sites (n = 5). PLAG1 IHC was diffusely strongly positive in 14/17 (82%) cases, whereas a single case of AMT diffusely expressed HMGA2. Both tumor groups showed PLAG1 gene fusions which were detected in 6/13 analyzable samples (AMT, n = 4 and CM, n = 2), and included TRPS1::PLAG1 (n = 3), NDRG1::PLAG1 (n = 1), CTNNB1::PLAG1 (n = 1) and a novel PXDNL::PLAG1 fusion (n = 1). The remaining 5 cases were negative, 5 were not analyzable and the single case positive for HMGA2 by IHC revealed a potential HMGA2 gene rearrangement. The cases were further studied by FISH, with 12/17 cases showing PLAG1 gene rearrangement (AMT, n = 8 and CM, n = 4). Altogether, 14/18 cases showed PLAG1 gene rearrangement by at least one of the methods. PLAG1 immunohistochemistry had a 92% specificity and sensitivity. Our study provided additional data to suggest that AMT and CM share overlapping morphological and immunohistochemical features as well as molecular background characterized by PLAG1 gene fusions and thus represent a morphological spectrum. In addition, we identified a novel PXDNL::PLAG1 fusion and suggested that rare cases may harbor HMGA2 gene alterations which seem to be mutually exclusive with PLAG1 gene fusions. The relatedness of these tumors to salivary gland myoepithelial neoplasms and distinctness from eccrine mixed tumors and other skin and soft tissue myoepithelial neoplasms with EWSR1/FUS fusions is discussed.
- Klíčová slova
- HMGA2, PLAG1, Apocrine mixed tumors, Cutaneous myoepitheliomas, Myoepithelial neoplasm, Targeted RNA sequencing,
- MeSH
- apokrinní žlázy * patologie MeSH
- DNA vazebné proteiny * genetika MeSH
- dospělí MeSH
- genová přestavba * MeSH
- hybridizace in situ fluorescenční MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- myoepiteliální nádor * genetika patologie chemie MeSH
- nádorové biomarkery * genetika analýza MeSH
- nádory kůže * genetika patologie chemie MeSH
- nádory potních žláz * genetika patologie MeSH
- protein HMGA2 * genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- DNA vazebné proteiny * MeSH
- HMGA2 protein, human MeSH Prohlížeč
- nádorové biomarkery * MeSH
- PLAG1 protein, human MeSH Prohlížeč
- protein HMGA2 * MeSH
Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.
- Klíčová slova
- Cancer Biology, Genomic Epidemiology, Integrative Multi-omics Analysis, Kidney Cancer, Tumour Microenvironment,
- MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- epigeneze genetická MeSH
- epitelo-mezenchymální tranzice * genetika MeSH
- glutathion-S-transferasa fí genetika metabolismus MeSH
- histonlysin-N-methyltransferasa genetika metabolismus MeSH
- karcinogeneze * genetika MeSH
- lidé MeSH
- metylace DNA * MeSH
- multiomika MeSH
- mutace * MeSH
- nádorové supresorové proteiny genetika metabolismus MeSH
- nádory ledvin * genetika patologie MeSH
- regulace genové exprese u nádorů MeSH
- stárnutí genetika MeSH
- thiolesterasa ubikvitinu MeSH
- transkripční faktory genetika metabolismus MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- BAP1 protein, human MeSH Prohlížeč
- DNA vazebné proteiny MeSH
- glutathion-S-transferasa fí MeSH
- GSTP1 protein, human MeSH Prohlížeč
- histonlysin-N-methyltransferasa MeSH
- nádorové supresorové proteiny MeSH
- PBRM1 protein, human MeSH Prohlížeč
- SETD2 protein, human MeSH Prohlížeč
- thiolesterasa ubikvitinu MeSH
- transkripční faktory MeSH
Stress responses play a vital role in cellular survival against environmental challenges, often exploited by cancer cells to proliferate, counteract genomic instability, and resist therapeutic stress. Heat shock factor protein 1 (HSF1), a central transcription factor in stress response pathways, exhibits markedly elevated activity in cancer. Despite extensive research into the transcriptional role of HSF1, the mechanisms underlying its activation remain elusive. Upon exposure to conditions that induce protein damage, monomeric HSF1 undergoes rapid conformational changes and assembles into trimers, a key step for DNA binding and transactivation of target genes. This study investigates the role of HSF1 as a sensor of proteotoxic stress conditions. Our findings reveal that purified HSF1 maintains a stable monomeric conformation independent of molecular chaperones in vitro. Moreover, while it is known that heat stress triggers HSF1 trimerization, a notable increase in trimerization and DNA binding was observed in the presence of protein-based crowders. Conditions inducing protein misfolding and increased protein crowding in cells directly trigger HSF1 trimerization. In contrast, proteosynthesis inhibition, by reducing denatured proteins in the cell, prevents HSF1 activation. Surprisingly, HSF1 remains activated under proteotoxic stress conditions even when bound to Hsp70 and Hsp90. This finding suggests that the negative feedback regulation between HSF1 and chaperones is not directly driven by their interaction but is realized indirectly through chaperone-mediated restoration of cytoplasmic proteostasis. In summary, our study suggests that HSF1 serves as a molecular crowding sensor, trimerizing to initiate protective responses that enhance chaperone activities to restore homeostasis.
- MeSH
- DNA vazebné proteiny metabolismus chemie genetika MeSH
- lidé MeSH
- multimerizace proteinu MeSH
- proteiny tepelného šoku HSP70 metabolismus chemie MeSH
- reakce na tepelný šok MeSH
- sbalování proteinů * MeSH
- transkripční faktory tepelného šoku * metabolismus genetika chemie MeSH
- transkripční faktory metabolismus chemie MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- HSF1 protein, human MeSH Prohlížeč
- proteiny tepelného šoku HSP70 MeSH
- transkripční faktory tepelného šoku * MeSH
- transkripční faktory MeSH
With the expanding possibilities of human genome research in recent years, the number of cases of soft tissue tumors that we are able to classify into the correct subgroups and to reveal their molecular profile is increasing. Among such tumors, we can also consider neoplasms that have a specific fusion of genes, in our case namely the pleomorphic adenoma gene 1 (PLAG1) and its partner. PLAG1 gene fusions were previously associated mainly with salivary gland pleomorphic adenomas, lipoblastomas, myoepithelial tumors, uterine epitheloid, myxoid leiomyosarcomas, and, recently, with PLAG1-rearranged fibromyxoid soft tissue tumors. To our knowledge, we report the first case of a soft tissue tumor with a PLAG1 fusion gene in an adult. In our case, we detected a new H3-3B::PLAG1 fusion in a soft tissue tumor, which originally appeared as nodular fasciitis.
- Klíčová slova
- H3‐3B, PLAG1, NGS, fibromyxoid soft tissue tumor, mesenchymal neoplasm, nodular fasciitis,
- MeSH
- DNA vazebné proteiny * genetika MeSH
- dospělí MeSH
- fibrom genetika patologie MeSH
- fúze genů MeSH
- fúzní onkogenní proteiny genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory měkkých tkání * genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- DNA vazebné proteiny * MeSH
- fúzní onkogenní proteiny MeSH
- PLAG1 protein, human MeSH Prohlížeč
The MRE11, RAD50, and NBN genes encode the MRN complex sensing DNA breaks and directing their repair. While carriers of biallelic germline pathogenic variants (gPV) develop rare chromosomal instability syndromes, the cancer risk in heterozygotes remains controversial. We performed a systematic review and meta-analysis of 53 studies in patients with different cancer diagnoses to better understand the cancer risk. We found an increased risk (odds ratio, 95% confidence interval) for gPV carriers in NBN for melanoma (7.14; 3.30-15.43), pancreatic cancer (4.03; 2.14-7.58), hematological tumors (3.42; 1.14-10.22), and prostate cancer (2.44, 1.84-3.24), but a low risk for breast cancer (1.29; 1.00-1.66) and an insignificant risk for ovarian cancer (1.53; 0.76-3.09). We found no increased breast cancer risk in carriers of gPV in RAD50 (0.93; 0.74-1.16; except of c.687del carriers) and MRE11 (0.87; 0.66-1.13). The secondary burden analysis compared the frequencies of gPV in MRN genes in patients from 150 studies with those in the gnomAD database. In NBN gPV carriers, this analysis additionally showed a high risk for brain tumors (5.06; 2.39-9.52), a low risk for colorectal (1.64; 1.26-2.10) and hepatobiliary (2.16; 1.02-4.06) cancers, and no risk for endometrial, and gastric cancer. The secondary burden analysis showed also a moderate risk for ovarian cancer (3.00; 1.27-6.08) in MRE11 gPV carriers, and no risk for ovarian and hepatobiliary cancers in RAD50 gPV carriers. These findings provide a robust clinical evidence of cancer risks to guide personalized clinical management in heterozygous carriers of gPV in the MRE11, RAD50, and NBN genes.
- Klíčová slova
- MRE11, NBN, RAD50, germline variants, meta‐analysis,
- MeSH
- DNA vazebné proteiny genetika MeSH
- enzymy opravy DNA genetika MeSH
- genetická predispozice k nemoci * MeSH
- homologní protein MRE11 * genetika MeSH
- hydrolasy působící na anhydridy kyselin * genetika MeSH
- jaderné proteiny * genetika MeSH
- lidé MeSH
- nádory * genetika MeSH
- proteiny buněčného cyklu * genetika MeSH
- zárodečné mutace * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- enzymy opravy DNA MeSH
- homologní protein MRE11 * MeSH
- hydrolasy působící na anhydridy kyselin * MeSH
- jaderné proteiny * MeSH
- MRE11 protein, human MeSH Prohlížeč
- NBN protein, human MeSH Prohlížeč
- proteiny buněčného cyklu * MeSH
- RAD50 protein, human MeSH Prohlížeč
Homologous recombination (HR) factors are crucial for DSB repair and processing stalled replication forks. RAD51 paralogs, including RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3, have emerged as essential tumour suppressors, forming two subcomplexes, BCDX2 and CX3. Mutations in these genes are associated with cancer susceptibility and Fanconi anaemia, yet their biochemical activities remain unclear. This study reveals a linear arrangement of BCDX2 subunits compared to the RAD51 ring. BCDX2 shows a strong affinity towards single-stranded DNA (ssDNA) via unique binding mechanism compared to RAD51, and a contribution of DX2 subunits in binding branched DNA substrates. We demonstrate that BCDX2 facilitates RAD51 loading on ssDNA by suppressing the cooperative requirement of RAD51 binding to DNA and stabilizing the filament. Notably, BCDX2 also promotes RAD51 loading on short ssDNA and reversed replication fork substrates. Moreover, while mutants defective in ssDNA binding retain the ability to bind branched DNA substrates, they still facilitate RAD51 loading onto reversed replication forks. Our study provides mechanistic insights into how the BCDX2 complex stimulates the formation of BRCA2-independent RAD51 filaments on short stretches of ssDNA present at ssDNA gaps or stalled replication forks, highlighting its role in genome maintenance and DNA repair.
- MeSH
- DNA vazebné proteiny * metabolismus genetika MeSH
- jednovláknová DNA * metabolismus genetika MeSH
- lidé MeSH
- multiproteinové komplexy MeSH
- mutace MeSH
- rekombinasa Rad51 * metabolismus genetika MeSH
- replikace DNA * genetika MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA vazebné proteiny * MeSH
- jednovláknová DNA * MeSH
- multiproteinové komplexy MeSH
- RAD51 protein, human MeSH Prohlížeč
- rekombinasa Rad51 * MeSH
