Search results for PRDM9

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Protein (1 results from a total of 1)

Identifier: R-HSA-912345
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: PRDM9: Q9NQV7

Reaction (3 results from a total of 3)

Identifier: R-HSA-1214188
Species: Homo sapiens
Compartment: nucleoplasm
As inferred from experiments in vitro with mouse Prdm9, human PRDM9 methylates histone H3 dimethylated at lysine-4 to yield histone H3 trimethylated at lysine-4.
Identifier: R-HSA-912363
Species: Homo sapiens
Compartment: nucleoplasm
PR-domain containing 9 (PRDM9) protein is a meiosis specific histone H3 lysine 4 (H3K4) methyltransferase, with a zinc finger domain at the C-terminus. Meiotic recombination hotspots in humans and mice are known to be sites for histone modification. PRDM9 has been shown to affect recombination profiles and meiotic recombination hotspot activity, by binding specific sequence motifs within or close to recombination hotspots (Baudat et al. 2010, Myers et al. 2010), and reorganizing chromatin structure. Variation within this protein has been proven to negatively affect human male fertility, with certain patients harboring variants at the PRDM9 locus exhibiting azoospermia. PRDM9 recognizes a specific sequence motif, but also acts at human hotspots lacking the motif, suggesting it is capable of acting in cis to regulate hotspot activity.
These specific sequence motifs also appear to be species specific, as the degenerate 13-bp motif associated with 40% of human hotspots does not function in chimpanzees, probably as a result of the rapidly evolving zinc finger domain (Myers et al. 2010). Subtle changes in the zinc finger array in humans can have global effects on recombination throughout the human genome, enhancing or decreasing the activity of a hotspot, or even creating entirely new hotspots (Berg et al. 2010). In addition to its role in regulating recombination hotspot activity, PRDM9 also appears to have a role in maintaining stability within the human genome, as variation in the PRDM9 gene can lead to large-scale genomic rearrangements and minisatellite instability in humans.
Identifier: R-HSA-5244692
Species: Homo sapiens
Compartment: nucleoplasm
Trimethylation of lysine-5 of histone H3 (H3K4) has been linked to transcriptional activation in a variety of eukaryotic species (Ruthenberg et al. 2007). Several H3K4 methyltransferases have been identified in mammals, predominantly members of the Mixed Lineage Leukemia (MLL) protein family. Five of these, KMT2A (MML1), KMT2D (MLL2), KMT2C (MLL3), KMT2B (MLL4) and SETD1A (KMT2F) have been shown to display H3K4 mono-, di- and tri-methyltransferase activity (Milne et al. 2002, Hughes et al. 2004, Cho et al. 2007, Wysocka et al. 2003). KMT2G (SETD1B) is believed to have similar activity on the basis of sequence homology (Ruthenberg et al. 2007). MLLs are a component of large multiprotein complexes that also include WDR5, RBBP5, ASH2 and DPY30, assembled to form the core MLL complex (Nakamura et al. 2002, Hughes et al. 2004, Dou et al. 2006, Tremblay et al. 2014). The WD40 domain of WDR5 recognizes and binds the histone H3 N-terminus, presenting the lysine-4 side chain for methylation by one of the catalytically active MLL family (Couture et al. 2006, Ruthenburg et al. 2006). Histone H3 recognition by WDR5 is regulated by the methylation state of the adjacent arginine (H3R2) residue. H3R2 methylation abolishes WDR5 interaction with the H3 histone tail (Couture et al. 2006); H3K4 di-/trimethylation and H3R2 methylation have an inverse relationship (Guccione et al. 2006).

SMYD3 (KMT3E) and PRDM9 (KMT8B) are able to tri-methylate H3K4 (Hamamoto et al. 2004, Hayashi et al. 2005, Koh-Stenta et al. 2014).

Set (1 results from a total of 1)

Identifier: R-HSA-5637685
Species: Homo sapiens
Compartment: nucleoplasm

Complex (1 results from a total of 1)

Identifier: R-HSA-912415
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (1 results from a total of 1)

Identifier: R-HSA-912446
Species: Homo sapiens
Compartment: nucleoplasm
Meiotic recombination exchanges segments of duplex DNA between chromosomal homologs, generating genetic diversity (reviewed in Handel and Schimenti 2010, Inagaki et al. 2010, Cohen et al. 2006). There are two forms of recombination: non-crossover (NCO) and crossover (CO). In mammals, the former is required for correct pairing and synapsis of homologous chromosomes, while CO intermediates called chiasmata are required for correct segregation of bivalents.
Meiotic recombination is initiated by double-strand breaks created by SPO11, which remains covalently attached to the 5' ends after cleavage. SPO11 is removed by cleavage of single DNA strands adjacent to the covalent linkage. The resulting 5' ends are further resected to produce protruding 3' ends. The single-stranded 3' ends are bound by RAD51 and DMC1, homologs of RecA that catalyze a search for homology between the bound single strand and duplex DNA of the chromosomal homolog. RAD51 and DMC1 then catalyze the invasion of the single strand into the homologous duplex and the formation of a D-loop heteroduplex. Approximately 90% of heteroduplexes are resolved without crossovers (NCO), probably by synthesis-dependent strand annealing.
The invasive strand is extended along the homolog and ligated back to its original duplex, creating a double Holliday junction. The mismatch repair proteins MSH4, MSH5 participate in this process, possibly by stabilizing the duplexes. The mismatch repair proteins MLH1 and MLH3 are then recruited to the double Holliday structure and an unidentified resolvase (Mus81? Gen1?) cleaves the junctions to yield a crossover.
Crossovers are not randomly distributed: The histone methyltransferase PRDM9 recruits the recombination machinery to genetically determined hotspots in the genome and each incipient crossover somehow inhibits formation of crossovers nearby, a phenomenon called crossover interference. Each chromosome bivalent, including the X-Y body in males, has at least one crossover and this is required for meiosis to proceed correctly.

For review, please refer to Cohen et al. 2006, Inagaki et al. 2010, Handel and Schimenti 2010.

The complex of FIRRM and FIGNL1 has recently been reported to bind to DMC1 and inhibit formation of meiotic crossovers (Fernandes et al. 2018).
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