title: The interaction between CtIP and BRCA1 is not essential for resection-mediated DNA repair or tumor suppression.
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 BRCA1 tumor suppressor, which interacts with CtIP in a phospho-dependent 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.
authors.affiliation: Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Colleen R
authors.initials: CR
authors.lastname: Reczek
authors.forename: Matthias
authors.initials: M
authors.lastname: Szabolcs
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Stark
authors.forename: Thomas
authors.initials: T
authors.lastname: Ludwig
authors.forename: Richard
authors.initials: R
authors.lastname: Baer
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D020022:Genetic Predisposition to Disease; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051135:Rad51 Recombinase / Q000378:metabolism; D051716:Replication Protein A / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D051135:Rad51 Recombinase; D051716:Replication Protein A; C501070:RBBP8 protein, mouse; C495154:Rad51 protein, mouse