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RecombinasesMeiosisBRCA1 ProteinGenes, BRCA1BRCA2 ProteinGenes, BRCA2IntegrasesDNA NucleotidyltransferasesRecombination, GeneticNondisjunction, GeneticChromosome SegregationAttachment Sites, MicrobiologicalChromosome PairingSynaptonemal ComplexChromatidsCrossing Over, GeneticSpores, FungalRec A RecombinasesChromosomesMutationCentromereRad51 RecombinaseCell Cycle ProteinsOocytesSchizosaccharomyces pombe ProteinsChromosomes, FungalMolecular Sequence DataTrisomySchizosaccharomycesMetaphaseSpindle ApparatusSaccharomyces cerevisiaeChromosomal Proteins, Non-HistoneChromosomes, PlantTransposon ResolvasesMitosisModels, GeneticBase SequenceNuclear ProteinsAmino Acid SequenceDNA, CruciformSpermatocytesDNA-Binding ProteinsBacteriophage lambdaSaccharomyces cerevisiae ProteinsMeiotic Prophase IGerm-Line MutationPotassium PermanganateEscherichia coliProphaseBreast NeoplasmsDNA Topoisomerases, Type IDNABacteriophagesEscherichia coli ProteinsTransposasesBinding SitesDNA, BacterialDNA RepairPlasmidsOvarian NeoplasmsChromosome MappingDNA Transposable ElementsSpermatogenesisDNA CleavageChromosomes, BacterialPachytene StageGenetic EngineeringSequence Homology, Amino AcidVirus IntegrationHeterozygoteBacterial ProteinsDNA, Single-StrandedSubstrate SpecificityCatalytic DomainViral ProteinsOogenesisJewsProtein Structure, TertiaryTyrosineGenetic TestingChromosome InversionHaploidyGene TargetingConserved SequenceSequence AlignmentCloning, MolecularProtein BindingCatalysisGerm CellsModels, MolecularGenetic Complementation TestMutagenesis, Site-DirectedNucleic Acid ConformationDNA, SuperhelicalTestisProtein EngineeringDNA Breaks, Double-StrandedDNA HelicasesMutagenesis, Insertional

Breast and ovarian cancerRad51 RecombinaseDMC1ProteinSsDNAHSF2BPOvarianMutationsMeiotic recombinationNuclearComplexREPAIRFoundRoleDevelopmentRAD51BRCA1 and BRCA2Homologous recombinationBinding proteinVariantsPALB2ProteinsGeneticMiceFunctionsHumanMouse

Breast and ovarian cancer2

• Germline mutations in BRCA2 predispose to breast and ovarian cancer with its predominant tumour suppressor function thought to be the repair of DNA double-strand breaks. (prolekarniky.cz)
• Germline mutations in BRCA2 predispose to both breast and ovarian cancer making it a good candidate gene for prostate cancer etiology. (prolekarniky.cz)

Rad51 Recombinase1

• Outside of plants and vertebrates, a much broader diversity of Rad51 recombinase paralog proteins exists. (wikipedia.org)

DMC13

• All of these proteins, with the exception of meiosis-specific DMC1, are essential for development in mammals. (wikipedia.org)
• In meiotic homologous recombination (HR), BRCA2 facilitates loading of the recombinases RAD51 and DMC1 at the sites of double-strand breaks (DSBs). (bvsalud.org)
• DMC1 is a necessary meiotic specific protein for homologous chromosome pairing and recombinant repair during meiosis. (nefu.edu.cn)

Protein4

• This protein can interact with the ssDNA-binding protein RPA, BRCA2, PALB2 and RAD52. (wikipedia.org)
• Brca2 protein. (lookformedical.com)
• The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (lookformedical.com)
• A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination. (shibuyahiroki.com)

SsDNA1

• The resulting recombinase-coated ssDNA filaments can invade the homologous chromosome dsDNA, searching for a complementary sequence (chromosome pairing), which will foster genetic material exchange. (nature.com)

HSF2BP3

• The HSF2BP-BRME1 complex interacts with BRCA2. (bvsalud.org)
• We previously showed that, in somatic cancer cells ectopically producing HSF2BP, DNA damage can trigger HSF2BP-dependent degradation of BRCA2, which prevents HR. Here, we report that, upon binding to BRCA2, HSF2BP forms octameric rings that are able to interlock into a large ring-shaped 24-nucleotide oligomer. (bvsalud.org)
• We propose that, during meiosis, the control of HSF2BP-BRCA2 oligomerization by BRME1 ensures timely assembly of the ring complex that concentrates BRCA2 and controls its turnover, thus promoting HR. (bvsalud.org)

Ovarian1

• In fact, over 75 genes associated with POI have been implicated in ovarian development and meiosis [ 15 ]. (nature.com)

Mutations1

• BRCA2 has also been implicated in prostate cancer etiology, but it is unclear the impact that mutations in this gene have on prostate tumourigenesis. (prolekarniky.cz)

Meiotic recombination1

• The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells. (shibuyahiroki.com)

Nuclear2

• Dissecting the telomere-inner nuclear membrane interface formed in meiosis. (shibuyahiroki.com)
• Castration of Brca2;Trp53 mutant animals led to regression of PIN lesions, but atypical cells persisted that continued to proliferate and express nuclear androgen receptor. (prolekarniky.cz)

Complex1

• Structure of a meiosis-specific complex central to BRCA2 localization at recombination sites. (shibuyahiroki.com)

REPAIR1

• It also prevents BRCA2 degradation during interstrand DNA crosslink repair in Xenopus egg extracts. (bvsalud.org)

Found3

• The recombinase paralog rfs-1 is found in the round worm Caenorhabditis elegans, where it is not essential for homologous recombination. (wikipedia.org)
• Among archaea the RadB and RadC recombinase paralogs are found in many organisms belonging to Euryarchaeota while a broader diversity of related recombinase paralogs seem to be found in the Crenarchaea including Ral1, Ral2, Ral3, RadC, RadC1, and RadC2. (wikipedia.org)
• A Rec A recombinase found in eukaryotes. (lookformedical.com)

Role2

• These results provide new mechanistic insights into the role of RAD51B not only in meiosis but in the maintenance of somatic genome stability. (nature.com)
• Here we have undertaken a genetic analysis in the mouse to determine the role of Brca2 in the adult prostate. (prolekarniky.cz)

Development1

• This study provides evidence that Brca2 can act as a tumour suppressor in the prostate, and the model we describe should prove useful in the development of new therapeutic approaches. (prolekarniky.cz)

RAD517

• 22. Defects in recombination activity caused by somatic and germline mutations in the multimerization/BRCA2 binding region of human RAD51 protein. (nih.gov)
• 23. The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair. (nih.gov)
• 26. Architectural plasticity of human BRCA2-RAD51 complexes in DNA break repair. (nih.gov)
• Outside of plants and vertebrates, a much broader diversity of Rad51 recombinase paralog proteins exists. (wikipedia.org)
• The proteins encoded by these genes were found to interact with DNA recombinase RAD51, which alluded to their role in homologous recombination (HR). Loss of function mutations in these genes was shown to result in increased genomic instability, which suggested their role as caretakers of the genome. (nih.gov)
• Our functional studies in mESC showed that this interaction is critical for RAD51 recruitment and repair of DSBs by HR. Surprisingly, our functional studies in mice revealed that the interaction is dispensable for repair of DNA replication induced breaks as well as repair of DSBs during meiosis. (nih.gov)
• When bound to BRCA2, DSS1 has been reported to act as a DNA mimic and facilitate RAD51 recruitment by displacing Replication Protein A (RPA) from single-stranded (ss) DNA at DSBs. (nih.gov)

BRCA1 and BRCA26

• 35. BRCA1 and BRCA2 protect against oxidative DNA damage converted into double-strand breaks during DNA replication. (nih.gov)
• While there are many possible risk factors associated with the development of breast cancer, the best-established indicator is the inheritance of breast cancer susceptibility genes such as BRCA1 and BRCA2 . (nih.gov)
• In 1997, just a few years after the cloning of BRCA1 and BRCA2 , their role in the repair of double strand breaks (DSBs) was uncovered. (nih.gov)
• In an effort to reduce the mortality due to breast cancer through prevention and early diagnosis, sequencing-based genetic tests are available to identify BRCA1 and BRCA2 mutation carriers. (nih.gov)
• The overarching goal of my laboratory over the past two decades has been to understand the functional significance of variants of unknown clinical significance (VUS) identified in BRCA1 and BRCA2 using mouse models as well as mouse embryonic stem cells (mESC). (nih.gov)
• We have developed assays to functionally characterize BRCA1 and BRCA2 variants and use our findings, together with other available epidemiological, structural, functional and in silico prediction models to classify the variants as neutral or pathogenic. (nih.gov)

Homologous recombination5

• 24. A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination. (nih.gov)
• 36. Hyperthermia adds to trabectedin effectiveness and thermal enhancement is associated with BRCA2 degradation and impairment of DNA homologous recombination repair. (nih.gov)
• 37. Plasticity of BRCA2 function in homologous recombination: genetic interactions of the PALB2 and DNA binding domains. (nih.gov)
• 40. BRCA2 regulates homologous recombination in response to DNA damage: implications for genome stability and carcinogenesis. (nih.gov)
• The recombinase paralog rfs-1 is found in the round worm Caenorhabditis elegans, where it is not essential for homologous recombination. (wikipedia.org)

Binding protein1

• This protein can interact with the ssDNA-binding protein RPA, BRCA2, PALB2 and RAD52. (wikipedia.org)

Variants1

• Our laboratory has generated a number of mouse models to assess the effects of BRCA2 variants on growth and development, fertility and tumorigenesis. (nih.gov)

PALB21

• We have generated mice with a single amino acid substitution (Gly25Arg) in the PALB2 (Partner and localizer of BRCA2) binding domain of BRCA2 and showed the importance BRCA2-PALB2 interaction in the repair of DSBs by HR as well as protection of stalled replication forks. (nih.gov)

Proteins2

• All of these proteins, with the exception of meiosis-specific DMC1, are essential for development in mammals. (wikipedia.org)
• The extent to which a specific variant complements the lethality of mESC lacking endogenous Brca1 or Brca2 and the known functions of these proteins in DNA repair is used as a surrogate readout to decipher their association with risk of developing the disease. (nih.gov)

Genetic1

• We have undertaken genetic approaches for functional dissection by generating targeted mutations found in breast cancer patients into specific functional domains of BRCA2 in mice. (nih.gov)

Mice1

• Histone methyltransferase PRDM9 is not essential for meiosis in male mice. (nih.gov)

Functions1

• Interrogating the Functions of PRDM9 Domains in Meiosis. (nih.gov)

Human2

• We are developing CRISPR-Cas9 based high throughput functional assays for BRCA2 in humanized mESC that lack endogenous Brca2 but carry a single copy of full-length human BRCA2 transgene cloned in a bacterial artificial chromosome. (nih.gov)
• We have also examined the physiological significance of BRCA2-DSS1 (Deleted in split hand/split foot1) interaction using a knock-in mouse model with a leucine to proline change in codon 2431 (Leu2431Pro, equivalent to human Leu2510Pro), which weakens this interaction. (nih.gov)

Mouse1

• After the break: DSB end processing in mouse meiosis. (nih.gov)