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Showing posts with the label topoisomerase

Note: Dynamic behavior of DNA topoisomerase IIbeta in response to DNA double-strand breaks

Note: Dynamic behavior of DNA topoisomerase IIbeta in response to DNA double-strand breaks (doi: 10.1038/s41598-018-28690-6) DNA topoisomerase II (Topo II) -plays important roles in various cellular processes, such as replication, transcription, and chromosome segregation. DNA topology problems may also occur during DNA repair, the possible involvement of Topo II in this process remains to be fully investigated. rapid recruitment of EGFP-tagged Topo IIβ to the DSB site. Topo IIβ is highly mobile in the nucleus. The Topo II catalytic inhibitors ICRF-187 and ICRF-193 reduced the Topo IIβ mobility and thereby prevented Topo IIβ recruitment to DSBs. Furthermore, Topo IIβ knockout cells exhibited increased sensitivity to bleomycin and decreased DSB repair mediated by homologous recombination (HR), implicating the role of Topo Iiβ in HR-mediated DSB repair. DNA topoisomerase II (Topo II) is an ATP-dependent enzyme that resolves DNA topological problems, such as superco...

Note for: Molecular mechanisms of etoposide

Note for: Molecular mechanisms of etoposide (doi: 10.17179/excli2015-561) TopoII - introducing transient breaks in the DNA molecule. involved in fundamental biological processes such as DNA replication, transcription, DNA repair and chromatin remodeling. A tyrosine in the active site of the enzyme initiates the first transesterification and forms a covalent adduct with the phosphate in the backbone of the DNA molecule. TopoII can perform three kinds of reactions while DNA relaxation is in common to TopoI, catenation/decatenation and knotting/unknotting are TopoII specific. Etoposide poisons the TopoII cleavage complexes (TopoIIcc) and inhibits the second step of the reaction (i.e. DNA religation). Mammals have two TopoII isoenzymes, TopoIIa and beta that are differently regulated during cell growth. TopoIIalpha is a proliferation marker and is greatly elevated in tumor cells, beta isoenzyme is present in proliferating as well as postmitotic cells (cell not devide anymo...

Note: Topoisomerases as anticancer targets

Note: Topoisomerases as anticancer targets (doi: 10.1042/BCJ20160583) topoisomerase poisoning -- replication fork arrest and DSB formation. Side effect of topo-II -- development of secondary cancers and cardiotoxicity. There are two types of DNA topoisomerases, type I and type II. – Actually it should be 3? Type I topoisomerases break one DNA strand of duplex DNA to allow either the passage of the other DNA strand through the break or the rotation of downstream DNA duplex about the break, and then reseal the broken strand. Topo-I (each subtype has different mechanism); 1.TopoIA -- requires nick or single-stranded region to bind 2.TopoIB -- cleave one strand of duplex DNA 3.TopoIC -- cleave one strand of duplex DNA Type II topo isomerases alter the linking number in steps of two by breaking both DNA strands of duplex DNA. There are two subtypes of type II topoisomerases (working as homodimer), type IIA and type IIB. Each subtype of topoisomerase is ...