TY - JOUR
T1 - The γ-tubulin meshwork assists in the recruitment of PCNA to chromatin in mammalian cells
AU - Corvaisier, Matthieu
AU - Zhou, Jingkai
AU - Malycheva, Darina
AU - Cornella, Nicola
AU - Chioureas, Dimitrios
AU - Gustafsson, Nina
AU - Rosselló, Catalina Ana
AU - Ayora, Silvia
AU - Li, Tongbin
AU - Ekström-Holka, Kristina
AU - Jirström, Karin
AU - Lindström, Lisa
AU - Alvarado Kristensson, Maria
PY - 2021/6/22
Y1 - 2021/6/22
N2 - 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.
AB - 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.
U2 - 10.1038/s42003-021-02280-1
DO - 10.1038/s42003-021-02280-1
M3 - Article
C2 - 34158617
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
M1 - 767
ER -