Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability

Yumay Chen; Chi Fen Chen; Huai Chin Chiang; Michelle Pena; Rosaria Polci; Randy L. Wei; Robert A. Edwards; Donna E. Hansel; Phang Lang Chen; Daniel J. Riley

doi:10.1186/1476-4598-10-5

Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability

Yumay Chen, Chi Fen Chen, Huai Chin Chiang, Michelle Pena, Rosaria Polci, Randy L. Wei, Robert A. Edwards, Donna E. Hansel, Phang Lang Chen, Daniel J. Riley

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

Background: NEK1, the first mammalian ortholog of the fungal protein kinase never-in-mitosis A (NIMA), is involved early in the DNA damage sensing/repair pathway. A defect in DNA repair in NEK1-deficient cells is suggested by persistence of DNA double strand breaks after low dose ionizing radiation (IR). NEK1-deficient cells also fail to activate the checkpoint kinases CHK1 and CHK2, and fail to arrest properly at G1/S or G2/M-phase checkpoints after DNA damage.Results: We show here that NEK1-deficient cells suffer major errors in mitotic chromosome segregation and cytokinesis, and become aneuploid. These NEK1-deficient cells transform, acquire the ability to grow in anchorage-independent conditions, and form tumors when injected into syngeneic mice. Genomic instability is also manifest in NEK1 +/- mice, which late in life develop lymphomas with a much higher incidence than wild type littermates.Conclusion: NEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability.

Original language	English (US)
Article number	5
Journal	Molecular Cancer
Volume	10
DOIs	https://doi.org/10.1186/1476-4598-10-5
State	Published - Jan 10 2011

ASJC Scopus subject areas

Molecular Medicine
Oncology
Cancer Research

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10.1186/1476-4598-10-5

Cite this

@article{547d38de68dc473e8b2bf1b2e752ea94,

title = "Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability",

abstract = "Background: NEK1, the first mammalian ortholog of the fungal protein kinase never-in-mitosis A (NIMA), is involved early in the DNA damage sensing/repair pathway. A defect in DNA repair in NEK1-deficient cells is suggested by persistence of DNA double strand breaks after low dose ionizing radiation (IR). NEK1-deficient cells also fail to activate the checkpoint kinases CHK1 and CHK2, and fail to arrest properly at G1/S or G2/M-phase checkpoints after DNA damage.Results: We show here that NEK1-deficient cells suffer major errors in mitotic chromosome segregation and cytokinesis, and become aneuploid. These NEK1-deficient cells transform, acquire the ability to grow in anchorage-independent conditions, and form tumors when injected into syngeneic mice. Genomic instability is also manifest in NEK1 +/- mice, which late in life develop lymphomas with a much higher incidence than wild type littermates.Conclusion: NEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability.",

author = "Yumay Chen and Chen, {Chi Fen} and Chiang, {Huai Chin} and Michelle Pena and Rosaria Polci and Wei, {Randy L.} and Edwards, {Robert A.} and Hansel, {Donna E.} and Chen, {Phang Lang} and Riley, {Daniel J.}",

note = "Funding Information: This work was initiated at University of Texas Health Science at San Antonio, completed at University of California, Irvine, and supported by grants from the PKD foundation, the American Society of Nephrology, the National Kidney Foundation, and the NIH (R01-DK067339) to YC; a George M. O{\textquoteright}Brien Kidney Research Center grant from the NIH to YC (P50-DK061597, Hanna E. Abboud, Program Director); a grant from the NIH to DJR (R01-DK61626); and a postdoctoral fellowship from the PKD Foundation to RP. We thank Sergio Garcia for technical support, and a Veterans Administration Renal Research Excellence Award to the South Texas Veterans Health Care System, Audie L.",

year = "2011",

month = jan,

day = "10",

doi = "10.1186/1476-4598-10-5",

language = "English (US)",

volume = "10",

journal = "Molecular Cancer",

issn = "1476-4598",

publisher = "BioMed Central",

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TY - JOUR

T1 - Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability

AU - Chen, Yumay

AU - Chen, Chi Fen

AU - Chiang, Huai Chin

AU - Pena, Michelle

AU - Polci, Rosaria

AU - Wei, Randy L.

AU - Edwards, Robert A.

AU - Hansel, Donna E.

AU - Chen, Phang Lang

AU - Riley, Daniel J.

N1 - Funding Information: This work was initiated at University of Texas Health Science at San Antonio, completed at University of California, Irvine, and supported by grants from the PKD foundation, the American Society of Nephrology, the National Kidney Foundation, and the NIH (R01-DK067339) to YC; a George M. O’Brien Kidney Research Center grant from the NIH to YC (P50-DK061597, Hanna E. Abboud, Program Director); a grant from the NIH to DJR (R01-DK61626); and a postdoctoral fellowship from the PKD Foundation to RP. We thank Sergio Garcia for technical support, and a Veterans Administration Renal Research Excellence Award to the South Texas Veterans Health Care System, Audie L.

PY - 2011/1/10

Y1 - 2011/1/10

N2 - Background: NEK1, the first mammalian ortholog of the fungal protein kinase never-in-mitosis A (NIMA), is involved early in the DNA damage sensing/repair pathway. A defect in DNA repair in NEK1-deficient cells is suggested by persistence of DNA double strand breaks after low dose ionizing radiation (IR). NEK1-deficient cells also fail to activate the checkpoint kinases CHK1 and CHK2, and fail to arrest properly at G1/S or G2/M-phase checkpoints after DNA damage.Results: We show here that NEK1-deficient cells suffer major errors in mitotic chromosome segregation and cytokinesis, and become aneuploid. These NEK1-deficient cells transform, acquire the ability to grow in anchorage-independent conditions, and form tumors when injected into syngeneic mice. Genomic instability is also manifest in NEK1 +/- mice, which late in life develop lymphomas with a much higher incidence than wild type littermates.Conclusion: NEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability.

AB - Background: NEK1, the first mammalian ortholog of the fungal protein kinase never-in-mitosis A (NIMA), is involved early in the DNA damage sensing/repair pathway. A defect in DNA repair in NEK1-deficient cells is suggested by persistence of DNA double strand breaks after low dose ionizing radiation (IR). NEK1-deficient cells also fail to activate the checkpoint kinases CHK1 and CHK2, and fail to arrest properly at G1/S or G2/M-phase checkpoints after DNA damage.Results: We show here that NEK1-deficient cells suffer major errors in mitotic chromosome segregation and cytokinesis, and become aneuploid. These NEK1-deficient cells transform, acquire the ability to grow in anchorage-independent conditions, and form tumors when injected into syngeneic mice. Genomic instability is also manifest in NEK1 +/- mice, which late in life develop lymphomas with a much higher incidence than wild type littermates.Conclusion: NEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability.

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VL - 10

JO - Molecular Cancer

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ER -

Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability

Abstract

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