Rac1 GTPase-deficient HeLa cells present reduced DNA repair, proliferation, and survival under UV or gamma irradiation

Molecular and Cellular Biochemistry
Gisele EspinhaFabio L Forti

Abstract

Rac1 GTPase controls essential cellular functions related to the cytoskeleton, such as motility and adhesion. Rac1 is overexpressed in many tumor cells, including breast cancers, where it is also involved in the proliferation and checkpoint control necessary for the cell's recovery after exposure to ionizing radiation. However, its role in DNA damage and repair remains obscure in other tumor cells and under different genotoxic conditions. Here, we compare HeLa cells with mutants exogenously expressing a dominant-negative Rac1 (HeLa-Rac1-N17) by their responses to DNA damage induced by gamma or UV radiation. In HeLa cells, these treatments led to increased levels of active Rac1 (Rac1-GTP) and of stress fibers, with a diminished ability to migrate compared to untreated cells. However, the reduction of Rac1-GTP in Rac1-N17-deficient clones resulted in much higher levels of polymerized stress fibers accompanied by a strong impairment of cell migration, even after both radiation treatments. With regard to proliferation and genomic stability, dominant-negative Rac1 cells were more sensitive to gamma and UV radiation, exhibiting reduced proliferation and survival consistent with increased DNA damage and delayed or reduced DNA repair o...Continue Reading

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Citations

Jan 30, 2016·Oxidative Medicine and Cellular Longevity·Gisele EspinhaFabio Luis Forti
Jul 21, 2016·Molecular and Cellular Biochemistry·Nirupama ChatterjeeGayatri Ramakrishna
Aug 11, 2020·Cancer Metastasis Reviews·Rui-Jie ZengEn-Min Li
Oct 30, 2016·Clinical Genetics·T ZouZ Liu
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Yuli T MagalhaesFabio L Forti
Mar 31, 2019·Molecular Cancer Therapeutics·Erik T GokaMarc E Lippman

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