BRCA1 participates in DNA decatenation

Zhenkun Lou, Katherine Minter-Dykhouse, Junjie Chen

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

The tumor suppressor BRCA1 has an important function in the maintenance of genomic stability. Increasing evidence suggests that BRCA1 regulates cell cycle checkpoints and DNA repair after DNA damage. However, little is known about its normal function in the absence of DNA damage. Here we show that BRCA1 interacts and colocalizes with topoisomerase IIα in S phase cells. Similar to cells treated with the topoisomerase IIα inhibitor ICRF-193, BRCA1-deficient cells show lagging chromosomes, indicating a defect in DNA decatenation and chromosome segregation. More directly, BRCA1 deficiency results in defective DNA decatenation in vitro. Finally, topoisomerase IIα is ubiquitinated in a BRCA1-dependent manner, and topoisomerase IIα ubiquitination correlates with higher DNA decatenation activity. Together these results suggest an important role of BRCA1 in DNA decatenation and reveal a previously unknown function of BRCA1 in the maintenance of genomic stability.

Original languageEnglish (US)
Pages (from-to)589-593
Number of pages5
JournalNature Structural and Molecular Biology
Volume12
Issue number7
DOIs
StatePublished - Jul 2005

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Type II DNA Topoisomerase
Genomic Instability
DNA
DNA Damage
Maintenance
Topoisomerase II Inhibitors
Chromosome Segregation
Ubiquitination
Cell Cycle Checkpoints
S Phase
DNA Repair
Chromosomes
Neoplasms

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

BRCA1 participates in DNA decatenation. / Lou, Zhenkun; Minter-Dykhouse, Katherine; Chen, Junjie.

In: Nature Structural and Molecular Biology, Vol. 12, No. 7, 07.2005, p. 589-593.

Research output: Contribution to journalArticle

Lou, Zhenkun ; Minter-Dykhouse, Katherine ; Chen, Junjie. / BRCA1 participates in DNA decatenation. In: Nature Structural and Molecular Biology. 2005 ; Vol. 12, No. 7. pp. 589-593.
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