The interaction between CtIP and BRCA1 is not essential for resection-mediated DNA repair or tumor suppression

Colleen R. Reczek, Matthias Szabolcs, Jeremy M. Stark, Thomas Ludwig, Richard Baer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

The CtIP protein facilitates homology-directed repair (HDR) of double-strand DNA breaks (DSBs) by initiating DNA resection, a process in which DSB ends are converted into 3'-ssDNA overhangs. The BRCA 1 tumor suppressor, which interacts with CtIP in a phosphodependent manner, has also been implicated in DSB repair through the HDR pathway. It was recently reported that the BRCA1-CtIP interaction is essential for HDR in chicken DT40 cells. To examine the role of this interaction in mammalian cells, we generated cells and mice that express Ctip polypeptides (Ctip-S326A) that fail to bind BRCA1. Surprisingly, isogenic lines of Ctip-S326A mutant and wild-type cells displayed comparable levels of HDR function and chromosomal stability. Although Ctip-S326A mutant cells were modestly sensitive to topoisomerase inhibitors, mice expressing Ctip-S326A polypeptides developed normally and did not exhibit a predisposition to cancer. Thus, in mammals, the phospho-dependent BRCA1-CtIP interaction is not essential for HDR-mediated DSB repair or for tumor suppression.

Original languageEnglish (US)
Pages (from-to)693-707
Number of pages15
JournalJournal of Cell Biology
Volume201
Issue number5
DOIs
StatePublished - May 2013

ASJC Scopus subject areas

  • Cell Biology

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