Dmc1 is a meiosis-specific RecA homologue []. It is a recombinase required for interhomologue recombination and double-strand break repair during meiosis [, , , ].
This entry includes Mei5 from budding yeasts and SFR1 from animals and fission yeasts. Although the fission yeast Swi5-Sfr1 complex is critical for homologous recombination repair, the budding yeast counterpart Sae3-Mei5 complex is meiosis-specific, interacts with Dmc1, and promotes assembly of Dmc1 on meiotic chromosomes [].SFR is a component of the SWI5-SFR1 complex, a complex required for double-strand break repair via homologous recombination []. Mei5 is one of a pair of meiosis-specific proteins which facilitate the loading of Dmc1 on to Rad51 on DNA at double-strand breaks during recombination. Recombination is carried out by a large protein complex based around the two RecA homologues, Rad51 and Dmc1 []. This complex may play both a catalytic and a structural role in the interaction between homologous chromosomes during meiosis. Mei5 is seen to contain a coiled-coli region.
Homologous-pairing protein 2 (Hop2) is required for proper homologous pairing and efficient cross-over and intragenic recombination during meiosis [, , ].The mammalian HOP2 homologue, TBPIP, was first identified as a factor interacting with TBP-1, which binds to the human immunodeficiency virus, type 1 Tat protein []. Later, TBPIP was found to be an activator that specifically stimulates the homologous pairing catalyzed by DMC1 [].
Brme1 (also known as Meiok21) is a component of meiotic recombination bridges involved in meiotic double-strand break repair [, ]. The C-terminal domain of Brme1 physically interacts with the N-terminal domain of HSF2BP []. BRME1 facilitates the loading of RAD51 and DMC1 recombinases onto DSBs (DNA double-strand breaks) through interaction with MEILB2/HSF2BP and replacing ssDNA binding proteins []. Brme1 is highly expressed in mice testes and fetal ovaries. Knockout of Brme1 results in male mice infertility [].
Homologous-pairing protein 2 (Hop2) is required for proper homologous pairing and efficient cross-over and intragenic recombination during meiosis [, , ].The mammalian HOP2 homologue, TBPIP, was first identified as a factor interacting with TBP-1, which binds to the human immunodeficiency virus, type 1 Tat protein []. Later, TBPIP was found to be an activator that specifically stimulates the homologous pairing catalyzed by DMC1 []. This entry represents the winged helix domain found in Hop2.
This domain is found at the C-terminal region of Hop2 and Mnd1 proteins. In meiotic DNA recombination, the Hop2-Mnd1 complex promotes Dmc1-mediated single-stranded DNA (ssDNA) invasion into homologous chromosomes to form a synaptic complex. Hop2 (for homologous pairing; also known as TBPIP) is expressed specifically during meiosis, same as Mnd1 (for meiotic nuclear divisions 1). The C-terminal region of both Hop2 and Mnd1, folds into three α-helices that are interrupted by two short non-helical regions. These α-helices of the two proteins together form a parallel coiled coil that provides the major interface for heterodimer formation. The non-helical regions form substantially kinked junctions between adjacent leucine zippers: the LZ1-LZ2 and LZ2-LZ3 junctions.This domain is the C-terminal segment of Hop2 and Mnd1 which folds back onto the C-terminal leucine zipper (LZ3) to form a helical bundle-like structure, hence designated LZ3wCH (for LZ3 with capping helices). The LZ3wCH region plays a role in interacting with the Dmc1 nucleofilament [].
The breast cancer type 2 susceptibility protein (BRCA2) is a breast tumour suppressor involved in double-strand break repair and/or homologous recombination []. BRCA2 gene expression is regulated in a cell-cycle dependent manner and peak expression of BRCA2 mRNA occurring in S phase, suggesting BRCA2 may participate in regulating cell proliferation. BRCA2, and related protein BRCA1, have transcriptional activation potential and the two proteins are associated with the activation of double-strand break repair and/or homologous recombination. The two proteins have been shown to coexist and colocalize in a biochemical complex. BRCA2 has a number of 39 amino acid repeats []that are critical for binding to RAD51 (a key protein in DNA recombinational repair) and resistance to methyl methanesulphonate treatment [, , ]. There are eight repeats in BRCA2 designated as BRC1 to BRC8. BRC1, BRC2, BRC3, BRC4, BRC7, and BRC8 have high sequence identity and bind to Rad51, whereas BRC5 and BRC6 are less well conserved and are unable to bind Rad51 []. It has been suggested that BRCA2 plays a role in positioning Rad51 at the site of DNA repair or in removing Rad51 from DNA once repair has been completed.Mutations in BRCA1 and BRCA2 have been linked to an elevated risk of young onset breast cancer and confer a high risk of the disease through a dominantly inherited fashion []. BRCA2 mutations are typically microdeletions.Homologues exist in plants: the BRCA2A and BRCA2B proteins from Arabidopsis thalianaare required for repair of breaks in double-stranded DNA and homologous recombination and in the prophase stage of meiosis are required for formation of RAD51 and DMC1 foci in males [].
