BRCA1 participates in DNA decatenation

Zhenkun Lou, Katherine Minter-Dykhouse, Junjie Chen

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

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

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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