OBJECTIVE The aim of this study was to determine whether the activity of topoisomerase I (topo I), the target of the anti-neoplastic drug camptothecin (CPT), is elevated in cervical cancer and whether CPT can radiosensitize cervical tumors. METHODS The topo I activity of 11 normal cervix and 30 cervical carcinoma tumors was assayed by measuring the relaxation of supercoiled DNA. Subconfluent ...

DNA topoisomerase IIalpha (topo IIalpha) is an essential nuclear enzyme and its unique decatenation activity has been implicated in many aspects of chromosome dynamics such as chromosome replication and segregation during mitosis. Here we show that chromatin-associated protein HMGB1 (a member of the large family of HMG-box proteins with possible functions in DNA replication, transcription, reco...

DNA topoisomerase (topo) II inhibitors either stabilize DNA-topo II complexes by blocking DNA religation (e.g. etoposide) or block the enzyme's catalytic activity (e.g. dexrazoxane). The former class of drugs causes direct DNA damage through topo II, while the latter class does not, but both classes cause apoptosis. We cloned the Fas ligand (FasL) promoter and coupled it to the luciferase gene....

Chromosome partitioning in Escherichia coli is assisted by two interacting proteins, topoisomerase (topo) IV and MukB. MukB stimulates the relaxation of negative supercoils by topo IV; to understand the mechanism of their action and to define this functional interplay, we determined the crystal structure of a minimal MukB-topo IV complex to 2.3 Å resolution. The structure shows that the so-call...

OBJECTIVES To report on a novel IIF pattern specifically associated with antibodies to DNA topo I. METHODS A novel compound IF pattern, designated Scl-70 pattern, was characterized in routine ANA-HEp-2 IIF screening. Within the last 3 years, all serum samples presenting the Scl-70 pattern at the ANA-HEp2 IIF screening were tested for anti-topo I reactivity. Conversely, 16 serum samples with k...

INTRODUCTION The presence of anti-topoisomerase I (topo I) antibodies is a classic scleroderma (SSc) marker presumably associated with a unique clinical subset. Here the clinical association of anti-topo I was reevaluated in unselected patients seen in a rheumatology clinic setting. METHODS Sera from the initial visit in a cohort of unselected rheumatology clinic patients (n = 1,966, includin...

In eukaryotes, type 1A topoisomerases (topos) act with RecQ-like helicases to maintain the stability of the genome. Despite having been the first type 1A enzymes to be discovered, much less is known about the involvement of the E. coli topo I (topA) and III (topB) enzymes in genome maintenance. These enzymes are thought to have distinct cellular functions: topo I regulates supercoiling and R-lo...

Aims—The nuclear enzyme DNA topoisomerase II has been shown to be required for chromatin condensation and chromosomal segregation during mitosis; its isoform topo IIá is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relation of the expression of topo IIá to the biological behaviour of conventional urinary bladder cancer. Methods—Formalin fixe...

Fission Yeast DNA topoisomerase II (165 kD) consists of an enzymatically active 125-kD core, approximately 10-kD NH2-terminal and 30-kD COOH-terminal domains. The question addressed in the present study is what is the role of the topo II termini. Although deletion of either the NH2 or the COOH terminus is viable, deletion of both termini is lethal; the termini share an essential role for viabil...