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Nek1 silencing slows down DNA repair and blocks DNA damage-induced cell cycle arrest.

Authors :
Pelegrini, Alessandra Luíza
Moura, Dinara Jaqueline
Brenner, Bethânia Luise
Ledur, Pitia Flores
Maques, Gabriela Porto
Pegas Henriques, João Antònio
Saffi, Jenifer
Lenz, Guido
Source :
Mutagenesis; Sep2010, Vol. 25 Issue 5, p447-454, 8p, 1 Black and White Photograph, 4 Graphs
Publication Year :
2010

Abstract

Never in mitosis A (NIMA)-related kinases (Nek) are evolutionarily conserved proteins structurally related to the Aspergillus nidulans mitotic regulator NIMA. Nek1 is one of the 11 isoforms of the Neks identified in mammals. Different lines of evidence suggest the participation of Nek1 in response to DNA damage, which is also supported by the interaction of this kinase with proteins involved in DNA repair pathways and cell cycle regulation. In this report, we show that cells with Nek1 knockdown (KD) through stable RNA interference present a delay in DNA repair when treated with methyl-methanesulfonate (MMS), hydrogen peroxide (H<subscript>2</subscript>O<subscript>2</subscript>) and cisplatin (CPT). In particular, interstrand cross links induced by CPT take much longer to be resolved in Nek1 KD cells when compared to wild-type (WT) cells. InKDcells, phosphorylation of Chk1 in response to CPTwas strongly reduced. While WTcells accumulate in G<subscript>2</subscript>/M after DNA damage with MMS and H<subscript>2</subscript>O<subscript>2</subscript>, Nek1 KD cells do not arrest, suggesting that G<subscript>2</subscript>/M arrest induced by the DNA damage requires Nek1. Surprisingly, CPT-treated Nek1 KD cells arrest with a 4N DNA content similar to WT cells. This deregulation in cell cycle control in Nek1 KD cells leads to an increased sensitivity to genotoxic agents when compared to WT cells. These results suggest that Nek1 is involved in the beginning of the cellular response to genotoxic stress and plays an important role in preventing cell death induced by DNA damage. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02678357
Volume :
25
Issue :
5
Database :
Complementary Index
Journal :
Mutagenesis
Publication Type :
Academic Journal
Accession number :
53298020
Full Text :
https://doi.org/10.1093/mutage/geq026