PMID- 20501547
OWN - NLM
STAT- MEDLINE
DCOM- 20101201
LR  - 20211203
IS  - 1464-3804 (Electronic)
IS  - 0267-8357 (Linking)
VI  - 25
IP  - 5
DP  - 2010 Sep
TI  - Nek1 silencing slows down DNA repair and blocks DNA damage-induced cell cycle 
      arrest.
PG  - 447-54
LID - 10.1093/mutage/geq026 [doi]
AB  - 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(2)O(2)) 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. In KD cells, phosphorylation of Chk1 in response to CPT was strongly 
      reduced. While WT cells accumulate in G(2)/M after DNA damage with MMS and 
      H(2)O(2), Nek1 KD cells do not arrest, suggesting that G(2)/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.
FAU - Pelegrini, Alessandra Luiza
AU  - Pelegrini AL
AD  - Department of Biophysics, Federal University of Rio Grande do Sul, Avenida Bento 
      Goncalves, 9500, Porto Alegre, RS, Brazil.
FAU - Moura, Dinara Jaqueline
AU  - Moura DJ
FAU - Brenner, Bethania Luise
AU  - Brenner BL
FAU - Ledur, Pitia Flores
AU  - Ledur PF
FAU - Maques, Gabriela Porto
AU  - Maques GP
FAU - Henriques, Joao Antonio Pegas
AU  - Henriques JA
FAU - Saffi, Jenifer
AU  - Saffi J
FAU - Lenz, Guido
AU  - Lenz G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100525
PL  - England
TA  - Mutagenesis
JT  - Mutagenesis
JID - 8707812
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (H2AX protein, human)
RN  - 0 (Histones)
RN  - 0 (Mutagens)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (CHEK1 protein, human)
RN  - EC 2.7.11.1 (Checkpoint Kinase 1)
RN  - EC 2.7.11.1 (NEK1 protein, human)
RN  - EC 2.7.11.1 (NIMA-Related Kinase 1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Camptothecin/pharmacology
MH  - *Cell Cycle/drug effects
MH  - Cell Cycle Proteins/*genetics/metabolism
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Checkpoint Kinase 1
MH  - Cross-Linking Reagents/metabolism
MH  - *DNA Damage
MH  - *DNA Repair/drug effects
MH  - G2 Phase/drug effects
MH  - Gene Knockdown Techniques
MH  - *Gene Silencing/drug effects
MH  - Histones/metabolism
MH  - Humans
MH  - Mutagens/toxicity
MH  - NIMA-Related Kinase 1
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/*deficiency/*genetics/metabolism
EDAT- 2010/05/27 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/05/27 06:00
PHST- 2010/05/27 06:00 [entrez]
PHST- 2010/05/27 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - geq026 [pii]
AID - 10.1093/mutage/geq026 [doi]
PST - ppublish
SO  - Mutagenesis. 2010 Sep;25(5):447-54. doi: 10.1093/mutage/geq026. Epub 2010 May 25.