SUMO-1 conjugation to human DNA topoisomerase II isozymes

Y Mao1, S D Desai, L F Liu

  • 1Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

Insights

DNA damage from teniposide causes small ubiquitin-related modifier (SUMO)-1 conjugation to topoisomerase II. This SUMO-1 modification of topoisomerase II also occurs with other stresses, suggesting a direct link to protein changes.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cell Biology

Background:

  • Topoisomerase I-mediated DNA damage induces small ubiquitin-related modifier (SUMO)-1 conjugation to topoisomerase I.
  • The role of SUMOylation in topoisomerase II activity and DNA damage response is not fully understood.

Purpose of the Study:

  • To investigate the effect of topoisomerase II-mediated DNA damage on SUMO-1 conjugation.
  • To explore the relationship between topoisomerase II conformation, DNA damage, and SUMO-1 conjugation.

Main Methods:

  • Utilized teniposide (VM-26) and ICRF-193 to induce DNA damage and conformational changes in topoisomerase II.
  • Employed immunological characterization and demonstrated physical interactions to identify SUMO-1 conjugates of topoisomerase II isozymes.
  • Applied oxidative and heat shock stresses to assess nuclear SUMO-1 conjugates.

Main Results:

  • Teniposide-induced DNA damage led to high molecular weight SUMO-1 conjugates of both topoisomerase IIalpha and IIbeta isozymes in HeLa cells.
  • Physical interaction between topoisomerase II and SUMO-1/UBC9 was demonstrated.
  • ICRF-193, without inducing DNA damage, also caused SUMO-1 conjugation to topoisomerase II isozymes.
  • Oxidative and heat shock stresses rapidly increased nuclear SUMO-1 conjugates.

Conclusions:

  • SUMO-1 conjugation is a rapid response to topoisomerase II-mediated DNA damage and also occurs upon conformational changes induced by agents like ICRF-193.
  • These findings suggest that SUMO-1 conjugation to topoisomerases may be a direct consequence of protein conformational changes rather than solely a DNA damage response.
  • Further investigation is needed to elucidate the precise mechanisms and functional implications of topoisomerase II SUMOylation.

Related Concept Videos

DNA Helicases00:55

DNA Helicases

DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
DNA Topoisomerases02:02

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types.  Type I...
Gene Conversion02:08

Gene Conversion

Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
Condensins02:15

Condensins

Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...