The gamma-tubulin meshwork assists in the recruitment of PCNA to chromatin in mammalian cells

摘要

Changes in the location of gamma-tubulin ensure cell survival and preserve genome integrity. We investigated whether the nuclear accumulation of gamma-tubulin facilitates the transport of proliferating cell nuclear antigen (PCNA) between the cytosolic and the nuclear compartment in mammalian cells. We found that the gamma-tubulin meshwork assists in the recruitment of PCNA to chromatin. Also, decreased levels of gamma-tubulin reduce the nuclear pool of PCNA. In addition, the gamma-tubulin C terminus encodes a PCNA-interacting peptide (PIP) motif, and a gamma-tubulin-PIP-mutant affects the nuclear accumulation of PCNA. In a cell-free system, PCNA and gamma-tubulin formed a complex. In tumors, there is a significant positive correlation between TUBG1 and PCNA expression. Thus, we report a novel mechanism that constitutes the basis for tumor growth by which the gamma-tubulin meshwork maintains indefinite proliferation by acting as an opportune scaffold for the transport of PCNA from the cytosol to the chromatin. Corvaisier et al discover that gamma-tubulin and replication protein PCNA forms a complex and that this facilitates recruitment of PCNA to chromatin both during cell division and during the DSB repair response. They identify a PCNA binding motif in gamma-tubulin, which when mutated affects replication fork progression, providing insights into the role of the nuclear gamma-tubulin meshwork.