The γ-tubulin meshwork assists in the recruitment of PCNA to chromatin in mammalian cells
Matthieu Corvaisier, Jingkai Zhou, Darina Malycheva, Nicola Cornella, Dimitrios Chioureas, Nina Gustafsson, Catalina Ana Rosselló, Silvia Ayora, Tongbin Li, Kristina Ekström‐Holka, Karin Jirström, Lisa Lindström, María Alvarado-Kristensson
Abstract
Changes in the location of γ-tubulin ensure cell survival and preserve genome integrity. We investigated whether the nuclear accumulation of γ-tubulin facilitates the transport of proliferating cell nuclear antigen (PCNA) between the cytosolic and the nuclear compartment in mammalian cells. We found that the γ-tubulin meshwork assists in the recruitment of PCNA to chromatin. Also, decreased levels of γ-tubulin reduce the nuclear pool of PCNA. In addition, the γ-tubulin C terminus encodes a PCNA-interacting peptide (PIP) motif, and a γ-tubulin-PIP-mutant affects the nuclear accumulation of PCNA. In a cell-free system, PCNA and γ-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 γ-tubulin meshwork maintains indefinite proliferation by acting as an opportune scaffold for the transport of PCNA from the cytosol to the chromatin.