User:Deh23/DMC1 (gene)

Article Draft
Meiotic recombination protein DMC1/LIM15 homolog is a protein that in humans is encoded by the DMC1 gene.

Mutations in this gene are associated with male sterility

RAD51 and DMC1 separated after a gene duplication event in the eukaryote common ancestor.

The presence of DMC1, not its activity is needed during meiosis. RAD51 acts to repair leftover DSBs after interhomolog recombination has occurred. RAD51 activity is down-regulated in budding yeast by inhibition of a Rad51-Rad54 complex through phosphorylation of Hed1 by the meiosis-specific recombinase Mek1.

Structure
Human DMC1 is a homomultimer in the form of an octameric ring with a diameter of 140 Å and a hole in the middle of 45 Å.  DMC1 binds preferentially to ssDNA over dsDNA. Unlike RecA and Rad51, DMC1 does not appear to form a helical filament on DNA, instead forming rings with DNA passing through the center. '''hDMC1 and hRAD51 have 54% amino acid similarity hDMC1 can conduct D-loop formation in supercoiled DNA DMC1 has weak ATPase activity, and is able to promote heteroduplex formation in the presence of a non-hydrolysable analog of ATP, indicating a requirement for ATP binding over ATP hydrolysis. '''

During meiosis, programmed DNA double strand breaks (DSBs) are introduced by topoisomerase-like enzyme Spo11. DSBs are lengthened through the actions of exonucleases to trim the 5' ends and form long 3' single-stranded DNA (ssDNA) overhangs. These 3' overhangs are stabilized by the effects of single strand binding proteins (SSBs) to protect the ssDNA and prevent the formation of secondary structures. DMC1 is loaded onto the 3' ssDNA to form a right-handed helical nucleoprotein filament. Subsequently, this nucleoprotein filament conducts a homology search in a homologous DNA region. Single-strand invasion in a complementary region in the homologous chromosome by the 3'-ended DNA strand forms a heteroduplex in the form of a displacement loop (D-loop). This D-Loop is extended as DNA repair synthesis occurs, forming a Holliday junction. Resolution of this Holiday junction results in crossover or non-crossover product.