NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response

Rosaria Polci, Aimin Peng, Phang Lang Chen, Daniel J. Riley, Yumay Chen

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Cellular functions of the NimA-related mammalian kinase Nek1 have not been demonstrated to date. Here we show that Nek1 is involved early in the DNA damage response induced by ionizing radiation (IR) and that Nek1 is important for cells to repair and recover from DNA damage. When primary or transformed cells are exposed to IR, Nek1 kinase activity is increased within 4 minutes, and Nek1 expression is up-regulated shortly thereafter and sustained for hours. At the same early time frame after IR that its kinase activity is highest, a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. There it colocalizes with γ-H2AX and NFBD1/MDC1, two key proteins involved very early in the response to IR-induced DNA double-strand breaks. Finally, Nek1-deficient fibroblasts are much more sensitive to the effects of IR-induced DNA damage than otherwise identical fibroblasts expressing Nek1. These results suggest that Nek1 may function as a kinase early in the DNA damage response pathway.

Original languageEnglish (US)
Pages (from-to)8800-8803
Number of pages4
JournalCancer Research
Volume64
Issue number24
DOIs
StatePublished - Dec 15 2004

Fingerprint

Ionizing Radiation
DNA Damage
Double-Stranded DNA Breaks
Phosphotransferases
Fibroblasts
Cytoplasm
NIMA-Related Kinase 1
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response. / Polci, Rosaria; Peng, Aimin; Chen, Phang Lang; Riley, Daniel J.; Chen, Yumay.

In: Cancer Research, Vol. 64, No. 24, 15.12.2004, p. 8800-8803.

Research output: Contribution to journalArticle

Polci, Rosaria ; Peng, Aimin ; Chen, Phang Lang ; Riley, Daniel J. ; Chen, Yumay. / NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response. In: Cancer Research. 2004 ; Vol. 64, No. 24. pp. 8800-8803.
@article{bfacb804c2bd428c835ab5db879e252f,
title = "NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response",
abstract = "Cellular functions of the NimA-related mammalian kinase Nek1 have not been demonstrated to date. Here we show that Nek1 is involved early in the DNA damage response induced by ionizing radiation (IR) and that Nek1 is important for cells to repair and recover from DNA damage. When primary or transformed cells are exposed to IR, Nek1 kinase activity is increased within 4 minutes, and Nek1 expression is up-regulated shortly thereafter and sustained for hours. At the same early time frame after IR that its kinase activity is highest, a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. There it colocalizes with γ-H2AX and NFBD1/MDC1, two key proteins involved very early in the response to IR-induced DNA double-strand breaks. Finally, Nek1-deficient fibroblasts are much more sensitive to the effects of IR-induced DNA damage than otherwise identical fibroblasts expressing Nek1. These results suggest that Nek1 may function as a kinase early in the DNA damage response pathway.",
author = "Rosaria Polci and Aimin Peng and Chen, {Phang Lang} and Riley, {Daniel J.} and Yumay Chen",
year = "2004",
month = "12",
day = "15",
doi = "10.1158/0008-5472.CAN-04-2243",
language = "English (US)",
volume = "64",
pages = "8800--8803",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "24",

}

TY - JOUR

T1 - NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response

AU - Polci, Rosaria

AU - Peng, Aimin

AU - Chen, Phang Lang

AU - Riley, Daniel J.

AU - Chen, Yumay

PY - 2004/12/15

Y1 - 2004/12/15

N2 - Cellular functions of the NimA-related mammalian kinase Nek1 have not been demonstrated to date. Here we show that Nek1 is involved early in the DNA damage response induced by ionizing radiation (IR) and that Nek1 is important for cells to repair and recover from DNA damage. When primary or transformed cells are exposed to IR, Nek1 kinase activity is increased within 4 minutes, and Nek1 expression is up-regulated shortly thereafter and sustained for hours. At the same early time frame after IR that its kinase activity is highest, a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. There it colocalizes with γ-H2AX and NFBD1/MDC1, two key proteins involved very early in the response to IR-induced DNA double-strand breaks. Finally, Nek1-deficient fibroblasts are much more sensitive to the effects of IR-induced DNA damage than otherwise identical fibroblasts expressing Nek1. These results suggest that Nek1 may function as a kinase early in the DNA damage response pathway.

AB - Cellular functions of the NimA-related mammalian kinase Nek1 have not been demonstrated to date. Here we show that Nek1 is involved early in the DNA damage response induced by ionizing radiation (IR) and that Nek1 is important for cells to repair and recover from DNA damage. When primary or transformed cells are exposed to IR, Nek1 kinase activity is increased within 4 minutes, and Nek1 expression is up-regulated shortly thereafter and sustained for hours. At the same early time frame after IR that its kinase activity is highest, a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. There it colocalizes with γ-H2AX and NFBD1/MDC1, two key proteins involved very early in the response to IR-induced DNA double-strand breaks. Finally, Nek1-deficient fibroblasts are much more sensitive to the effects of IR-induced DNA damage than otherwise identical fibroblasts expressing Nek1. These results suggest that Nek1 may function as a kinase early in the DNA damage response pathway.

UR - http://www.scopus.com/inward/record.url?scp=10844257527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10844257527&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-04-2243

DO - 10.1158/0008-5472.CAN-04-2243

M3 - Article

C2 - 15604234

AN - SCOPUS:10844257527

VL - 64

SP - 8800

EP - 8803

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 24

ER -