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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

NEK5 interacts with topoisomerase II beta and is involved in the DNA damage response induced by etoposide

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Author(s):
Melo-Hanchuk, Talita Diniz [1] ; Slepicka, Priscila Ferreira [2] ; Pelegrini, Alessandra Luiza [3] ; Martins Menck, Carlos Frederico [3] ; Kobarg, Jorg [4, 1]
Total Authors: 5
Affiliation:
[1] Univ Estadual Campinas, Inst Biol, Dept Bioquim & Biol Tecidual, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil
[2] Ctr Nacl Pesquisa Energia & Mat, Lab Nacl Biociencias, Campinas, SP - Brazil
[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo - Brazil
[4] Univ Estadual Campinas, Fac Ciencias Farmaceut, Campinas, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Journal of Cellular Biochemistry; v. 120, n. 10, p. 16853-16866, OCT 2019.
Web of Science Citations: 0
Abstract

Cells are daily submitted to high levels of DNA lesions that trigger complex pathways and cellular responses by cell cycle arrest, apoptosis, alterations in transcriptional response, and the onset of DNA repair. Members of the NIMA-related kinase (NEK) family have been related to DNA damage response and repair and the first insight about NEK5 in this context is related to its role in centrosome separation resulting in defects in chromosome integrity. Here we investigate the potential correlation between NEK5 and the DNA damage repair index. The effect of NEK5 in double-strand breaks caused by etoposide was accessed by alkaline comet assay and revealed that NEK5-silenced cells are more sensitive to etoposide treatment. Topoisomerase II beta (TOPII beta) is a target of etoposide that leads to the production of DNA breaks. We demonstrate that NEK5 interacts with TOPII beta, and the dynamics of this interaction is evaluated by proximity ligation assay. The complex NEK5/TOPII beta is formed immediately after etoposide treatment. Taken together, the results of our study reveal that NEK5 depletion increases DNA damage and impairs proper DNA damage response, pointing out NEK5 as a potential kinase contributor to genomic stability. (AU)

FAPESP's process: 14/15982-6 - Consequences of repair deficiencies in damaged genome
Grantee:Carlos Frederico Martins Menck
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 17/03489-1 - From functional studies to searching for new inhibitors for cancer: exploring kinases that regulate the cell cycle of the human NEK family
Grantee:Jörg Kobarg
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 10/51730-0 - Functional and structural studies of protein kinases involved in cancer and neglected diseases: towards the development of new inhibitors
Grantee:Jörg Kobarg
Support Opportunities: Regular Research Grants
FAPESP's process: 15/06458-4 - Functional characterization of regulatory proteins involved in DNA repair
Grantee:Talita Diniz Melo Hanchuk
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 10/16831-0 - Functional Characterization: The human kinase Nek5 interferes negatively in cell death and the polyglutamylation process
Grantee:Talita Diniz Melo Hanchuk
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 10/15262-2 - Cloning and expression of human protein kinase Nek10 structural and functional studies aimed at molecular and cellular
Grantee:Priscila Ferreira Papa
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)