title: Cdk1 and BRCA1 target γ-tubulin to microtubule domains.
abstract: DNA damage is a critical event that requires an appropriate cellular response. This is mediated by checkpoint proteins such as Cdk1 that controls S/G2 and G2/M transition. Cdk1 is required for BRCA1 transport to DNA damage sites inside the nucleus where BRCA1 functions as a scaffold to initiate a signaling cascade. BRCA1 is a multifunctional protein that also ubiquitinates γ-tubulin and, consequently, inhibits microtubule nucleation at the centrosome. Here, we report that γ-tubulin also localizes at confined areas in the microtubule network. Nocodazole-mediated microtubule depolymeration results in disappearance of this γ-tubulin fraction, while microtubule stabilization by taxol preserves this structure. Surprisingly, overexpression of Cdk1 or BRCA1 greatly expands the γ-tubulin coating of microtubules, suggesting that the microtubule-bound γ-tubulin is involved in DNA damage response. This is in accordance with numerous reports of microtubule-associated DNA damage proteins, such as p53, that are transported to the nucleus when DNA damage occurs. γ-Tubulin itself has been reported to form complexes with DNA repair proteins in the nucleus.
authors.affiliation: Department of Medical Protein Research, VIB, B-9000 Ghent, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hubert
authors.forename: Joël
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: Jan
authors.initials: J
authors.lastname: Gettemans
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D045744:Cell Line, Tumor; D004249:DNA Damage; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014404:Tubulin; D050257:Tubulin Modulators; D016203:CDC2 Protein Kinase; D015739:Nocodazole