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      Polo-like kinase-1 in DNA damage response

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          Abstract

          Polo-like kinase-1 (Plk1) belongs to a family of serine-threonine kinases and plays a critical role in mitotic progression. Plk1 involves in the initiation of mitosis, centrosome maturation, bipolar spindle formation, and cytokinesis, well-reported as traditional functions of Plk1. In this review, we discuss the role of Plk1 during DNA damage response beyond the functions in mitotsis. When DNA is damaged in cells under various stress conditions, the checkpoint mechanism is activated to allow cells to have enough time for repair. When damage is repaired, cells progress continuously their division, which is called checkpoint recovery. If damage is too severe to repair, cells undergo apoptotic pathway. If damage is not completely repaired, cells undergo a process called checkpoint adaptation, and resume cell division cycle with damaged DNA. Plk1 targets and regulates many key factors in the process of damage response, and we deal with these subjects in this review. [BMB Reports 2014; 47(5): 249-255]

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          Most cited references76

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          Live or let die: the cell's response to p53.

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            MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks.

            Histone variant H2AX phosphorylation in response to DNA damage is the major signal for recruitment of DNA-damage-response proteins to regions of damaged chromatin. Loss of H2AX causes radiosensitivity, genome instability, and DNA double-strand-break repair defects, yet the mechanisms underlying these phenotypes remain obscure. Here, we demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX (gammaH2AX) by specifically interacting with the phosphoepitope at the gammaH2AX carboxyl terminus. Moreover, through a combination of biochemical, cell-biological, and X-ray crystallographic approaches, we reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex. These data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is the major mediator of gammaH2AX recognition following DNA damage. We further show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX phosphorylation and is required for normal radioresistance and efficient accumulation of DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian response to DNA damage.
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              Polo-like kinases and the orchestration of cell division.

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                Author and article information

                Journal
                BMB Rep
                BMB Rep
                ksbmb
                BMB Reports
                Korean Society for Biochemistry and Molecular Biology
                1976-6696
                1976-670X
                May 2014
                : 47
                : 5
                : 249-255
                Affiliations
                Department of Nanobiomedical Science & BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Korea
                Author notes
                [* ]Corresponding author. Tel: +82-41-550-1936; Fax: +82-41-559-7839; E-mail: yjjang@ 123456dankook.ac.kr
                [# ]These authors have equally contributed.
                Article
                BMB-47-249
                10.5483/BMBRep.2014.47.5.061
                4163859
                24667170
                14a729d1-01ee-42b2-a37e-14af6e524696
                Copyright © 2014, Korean Society for Biochemistry and Molecular Biology

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 February 2014
                Categories
                Articles

                cell cycle,dna damage checkpoint,polo-like kinase-1,p53
                cell cycle, dna damage checkpoint, polo-like kinase-1, p53

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