| |
[摘要]：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 gamma-tubulin and, consequently, inhibits microtubule nucleation at the centrosome. Here, we report that gamma-tubulin also localizes at confined areas in the microtubule network. Nocodazole-mediated microtubule depolymeration results in disappearance of this gamma-tubulin fraction, while microtubule stabilization by taxol preserves this structure. Surprisingly, overexpression of Cdk1 or BRCA1 greatly expands the gamma-tubulin coating of microtubules, suggesting that the microtubule-bound gamma-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. gamma-Tubulin itself has been reported to form complexes with DNA repair proteins in the nucleus. (C) 2011 Elsevier Inc. All rights reserved. |
|
