TOP3A

DNA topoisomerase 3-alpha is an enzyme that in humans is encoded by the TOP3A gene.^[5][6]

TOP3A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4CGY, 4CHT
Identifiers
Aliases	TOP3A, TOP3, ZGRF7, topoisomerase (DNA) III alpha, DNA topoisomerase III alpha, PEOB5, MGRISCE2
External IDs	OMIM: 601243; MGI: 1197527; HomoloGene: 3394; GeneCards: TOP3A; OMA:TOP3A - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p11.2 Start 18,271,428 bp[1] End 18,315,007 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B2 Start 60,630,884 bp[2] End 60,668,191 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood ganglionic eminence ventricular zone bone marrow cells monocyte stromal cell of endometrium granulocyte tonsil epithelium of colon testicle Top expressed in spermatocyte zygote secondary oocyte spermatid tail of embryo primary oocyte Ileal epithelium genital tubercle epiblast seminiferous tubule More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA topoisomerase type I (single strand cut, ATP-independent) activity DNA binding zinc ion binding protein binding isomerase activity metal ion binding DNA topoisomerase activity single-stranded DNA binding nucleic acid binding Cellular component PML body nucleoplasm chromosome nucleus mitochondrion mitochondrial matrix Biological process DNA replication DNA topological change meiosis mitochondrial DNA metabolic process chromosome separation regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7156 21975 Ensembl ENSG00000284238 ENSG00000177302 ENSMUSG00000002814 UniProt Q13472 O70157 RefSeq (mRNA) NM_004618 NM_001320759 NM_009410 RefSeq (protein) NP_001307688 NP_004609 NP_033436 Location (UCSC) Chr 17: 18.27 – 18.32 Mb Chr 11: 60.63 – 60.67 Mb PubMed search [3] [4]
Wikidata
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Function

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells.^[6]

Meiosis

A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.

Recombination during meiosis is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at the 5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule then "invades" the DNA of an homologous chromosome that is not broken forming a displacement loop (D-loop). After strand invasion, the further sequence of events may follow either of two main pathways leading to a crossover (CO) or a non-crossover (NCO) recombinant (see Genetic recombination and see Figure). The pathway leading to a NCO is referred to as Synthesis-dependent strand annealing (SDSA).

In the plant Arabidopsis thaliana, multiple mechanisms limit meiotic COs.^[7] During meiosis TOP3A and RECQ4A/B helicase antagonize formation of COs in parallel to FANCM helicase.^[7] Sequela-Arnaud et al.^[7] suggested that CO numbers are restricted because of the long-term costs of CO recombination, that is, the breaking up of favorable genetic combinations of alleles built up by past natural selection.

In the budding yeast Saccharomyces cerevisiae, the topoisomerase III (TOP3)-RMI1 heterodimer (that catalyzes DNA single-strand passage) forms a conserved complex with Sgs1 helicase (an ortholog of the human Bloom syndrome helicase). This complex promotes early formation of NCO recombinants during meiosis^[8] The TOP3-RMI1 strand passage activity appears to have two important functions during meiosis.^[8] First, strand passage activity is employed early in coordination with Sgs1 helicase to promote proper recombination pathway choice. Second, strand passage activity is used later, independently of Sgs1 helicase, to prevent the persistence of unresolvable strand entanglements in recombination intermediates.

Interactions

TOP3A has been shown to interact with Bloom syndrome protein.^{[9][10][11][12]}