| TOP3A | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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DNA topoisomerase 3-alpha is an enzyme that in humans is encoded by the TOP3A gene. [5] [6]
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]
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.
TOP3A has been shown to interact with Bloom syndrome protein. [9] [10] [11] [12]
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two hybridized nucleic acid strands, using energy from ATP hydrolysis. There are many helicases, representing the great variety of processes in which strand separation must be catalyzed. Approximately 1% of eukaryotic genes code for helicases.
RecQ helicase is a family of helicase enzymes initially found in Escherichia coli that has been shown to be important in genome maintenance. They function through catalyzing the reaction ATP + H2O → ADP + P and thus driving the unwinding of paired DNA and translocating in the 3' to 5' direction. These enzymes can also drive the reaction NTP + H2O → NDP + P to drive the unwinding of either DNA or RNA.
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids.
Werner syndrome ATP-dependent helicase, also known as DNA helicase, RecQ-like type 3, is an enzyme that in humans is encoded by the WRN gene. WRN is a member of the RecQ Helicase family. Helicase enzymes generally unwind and separate double-stranded DNA. These activities are necessary before DNA can be copied in preparation for cell division. Helicase enzymes are also critical for making a blueprint of a gene for protein production, a process called transcription. Further evidence suggests that Werner protein plays a critical role in repairing DNA. Overall, this protein helps maintain the structure and integrity of a person's DNA.
DNA mismatch repair protein Mlh1 or MutL protein homolog 1 is a protein that in humans is encoded by the MLH1 gene located on chromosome 3. It is a gene commonly associated with hereditary nonpolyposis colorectal cancer. Orthologs of human MLH1 have also been studied in other organisms including mouse and the budding yeast Saccharomyces cerevisiae.
Ku80 is a protein that, in humans, is encoded by the XRCC5 gene. Together, Ku70 and Ku80 make up the Ku heterodimer, which binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair. It is also required for V(D)J recombination, which utilizes the NHEJ pathway to promote antigen diversity in the mammalian immune system.
Replication protein A 70 kDa DNA-binding subunit is a protein that in humans is encoded by the RPA1 gene.
DNA topoisomerase 2-beta is an enzyme that in humans is encoded by the TOP2B gene.
Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome.
Exonuclease 1 is an enzyme that in humans is encoded by the EXO1 gene.
DNA repair protein RAD51 homolog 4 is a protein that in humans is encoded by the RAD51L3 gene.
DNA repair protein XRCC2 is a protein that in humans is encoded by the XRCC2 gene.
ATP-dependent DNA helicase Q1 is an enzyme that in humans is encoded by the RECQL gene.
DNA topoisomerase 3-beta-1 is an enzyme that in humans is encoded by the TOP3B gene.
RecQ-mediated genome instability protein 1 is a protein that in humans is encoded by the RMI1 gene.
ATP-dependent DNA helicase Q5 is an enzyme that in humans is encoded by the RECQL5 gene.
DNA2-like helicase is an enzyme that in humans is encoded by the DNA2 gene. Dna2, a homolog of DNA2KL present in budding yeast, possesses both helicase and nuclease activity, with which it helps catalyze early steps in homologous recombination.
Sgs1, also known as slow growth suppressor 1, is a DNA helicase protein found in Saccharomyces cerevisiae. It is a homolog of the bacterial RecQ helicase. Like the other members of the RecQ helicase family, Sgs1 is important for DNA repair. In particular, Sgs1 collaborates with other proteins to repair double-strand breaks during homologous recombination in eukaryotes.
Synthesis-dependent strand annealing (SDSA) is a major mechanism of homology-directed repair of DNA double-strand breaks (DSBs). Although many of the features of SDSA were first suggested in 1976, the double-Holliday junction model proposed in 1983 was favored by many researchers. In 1994, studies of double-strand gap repair in Drosophila were found to be incompatible with the double-Holliday junction model, leading researchers to propose a model they called synthesis-dependent strand annealing. Subsequent studies of meiotic recombination in S. cerevisiae found that non-crossover products appear earlier than double-Holliday junctions or crossover products, challenging the previous notion that both crossover and non-crossover products are produced by double-Holliday junctions and leading the authors to propose that non-crossover products are generated through SDSA.
Crossover junction endodeoxyribonuclease, also known as Holliday junction resolvase, Holliday junction endonuclease, Holliday junction-cleaving endonuclease, Holliday junction-resolving endoribonuclease, crossover junction endoribonuclease, and cruciform-cutting endonuclease, is an enzyme involved in DNA repair and homologous recombination. Specifically, it performs endonucleolytic cleavage that results in single-stranded crossover between two homologous DNA molecules at the Holliday junction to produce recombinant DNA products for chromosomal segregation. This process is known as Holliday junction resolution.
