Disease relevance of DMC1

• In yeast an Escherichia coli RecA-like gene, DMC1, is expressed in meiotic prophase and its product co-localizes with Rad51 protein on zygotene chromosomes [1].
• We documented loss of expression of DMC1 in 2 of 10 breast-cancer cell lines, in 7 of 10 cervical-cancer lines, in 7 of 13 hepatocellular-cancer lines, in 3 of 7 lung-cancer lines, in 3 of 6 thyroid-cancer lines, in 2 of 6 gastric-cancer lines, and in 2 of 4 renal cell-cancer lines [2].
• DMC1: a monoclonal antibody produced from histiocytosis X cells which reacts with the native CD1a molecule of human epidermal Langerhans cells [3].
• We produced a murine MCA, called DMC1, after immunization with proliferating Langerhans cells of Eosinophilic Granuloma of the bone (Histiocytosis X) [3].

High impact information on DMC1

• The different pattern of localization of the Rad51 protein between the leptotene and pachytene stages and the absence of the Lim15 protein in the pachytene stage suggest that the Rad51 protein plays different roles in these stages [4].
• The presence of Rad51 and/or Lim15 proteins in early nodules supports the hypothesis that early nodules are involved in recombination-related events during meiosis [5].
• Eukaryotic cells require two homologs of Escherichia coli RecA protein, Rad51 and Dmc1, for meiotic recombination [6].
• This analysis allowed the exclusion of proposed candidate tumour suppressor genes including MLL septin-like fusion (MSF), survivin, and deleted in multiple human cancer (DMC1) [7].
• The domain II region, highly conserved in the E.coli RecA-like protein family, was also found in the mammalian DMC1 proteins, including the two ATP binding motifs and DNA binding sites with the region [1].

Biological context of DMC1

• Therefore, these results suggest that TBPIP/HOP2 directly binds to DNA and functions as an activator for DMC1 during the homologous pairing step in meiosis [8].
• During mouse meiosis, the early prophase RAD51/DMC1 recombination protein sites, which are associated with the chromosome cores and which serve as markers for ongoing DNA-DNA interactions, are in ten-fold excess of the eventual reciprocal recombinant events [9].
• The C-terminal domain (amino acid 234-340) of MmDMC1 binds to DNA-binding domain of p53 protein. p53 might be involved in homologous recombination and/or checkpoint function by directly binding to DMC1 protein to repress genomic instability in meiotic germ cells [10].
• The overall amino acid sequence reveals characteristic elements of a RECA-like gene yet harbors an src-like phosphorylation site curiously absent from hRAD51 and hLIM15 [11].
• The predicted amino acid sequence of the oyster mushroom gene is 62% identical to the yeast DMC1 and 60% identical to human DMC1 [12].

Anatomical context of DMC1

• Using the reverse transcriptase-polymerase chain reaction (RT-PCR) to examine cancer cell lines for alterations in the expression of transcripts from this portion of 17q, we identified a novel gene that we designated DMC1 (downregulated in multiple cancer-1) [2].
• BL6 and DMC1 MoAb interfered with an early event of T-cell activation, as shown by a time-course study [13].
• At the ultrastructural level, DMC1 MCA was specific for Birbeck granule-containing Langerhans cells and did not react with melanocyte and keratinocyte populations [3].
• In tissues DMC1 MCA reacted with epidermal dendritic cells (Langerhans cells) in the skin and cortical thymocytes in the thymus as observed on indirect immunofluorescence [3].
• In contrast, Dmc1 transcripts and the protein production were first detected at day 6 after hCG injection and increased along with the increment of spermatocytes [14].

Associations of DMC1 with chemical compounds

• Expression of various germ cell markers, such as Vasa, growth differentiation marker 9 and SSEA-1, increased in the clonal cell line, and OLCs showed additionally expression of meiosis-specific markers SCP3 and DMC1 [15].

Physical interactions of DMC1

• DNA topoisomerase II interacts with Lim15/Dmc1 in meiosis [16].

Regulatory relationships of DMC1

• Rad51 expresses in both mitotic and meiotic tissues whereas Dmc1 is confined to meiosis [17].

Other interactions of DMC1

• Intron conservation, intron gain or loss and putative intron sliding events were determined for a set of three genes (SPO11, MRE11 and DMC1) involved in basic aspects of recombination in eukaryotes [18].
• Emerging evidence suggests that the tumor suppressor BRCA2 functions in the assembly of nucleoprotein filaments of Rad51 and Dmc1 [19].
• We propose that the interaction between Lim15/Dmc1 and PCNA mediates the recombination-associated DNA synthesis during meiosis [20].
• A significant inhibition of the mixed skin cell-lymphocyte reaction was obtained with BL6 and DMC1 monoclonal antibodies (MoAb), which recognize the same epitope on CD1a molecule [13].
• Here, we show that Ubc9 interacts with the meiosis-specific RecA homolog, Lim15/Dmc1 in the basidiomycete Coprinus cinereus (CcLim15), and mediates sumoylation of CcLim15 during meiosis [21].

Analytical, diagnostic and therapeutic context of DMC1

• Analytical ultracentrifugation experiments revealed that, whereas full-length DMC1 forms a octamer, DMC1-(82-340) is a heptamer [22].
• Electron microscopy reveals that the human meiosis-specific recombinase Dmc1 forms ring structures that bind single-stranded (ss) and double-stranded (ds) DNA [23].
• Sequence analysis and biochemical studies have shown that archaeal RadA proteins are more closely related to Rad51 and Dmc1 than the bacterial RecA proteins [24].
• Analysis of protein-protein interactions using surface plasmon resonance indicates that Coprinus cinereus PCNA (CoPCNA) specifically interacts with a meiotic specific RecA-like factor, C. cinereus Lim15/Dmc1 (CoLim15) in vitro [20].
• The amino acid sequences encoded by the PCR fragments, three RadA protein sequences previously published (21), and two new complete RadA sequences were aligned with representative bacterial RecA proteins and eucaryal Rad51 and Dmc1 proteins [25].

References