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Heat shock factor 1, an inhibitor of non-homologous end joining repair

Title
Heat shock factor 1, an inhibitor of non-homologous end joining repair
Authors
Kang, Ga-YoungKim, Eun-HoLee, Hae-JuneGil, Na-YeonCha, Hyuk-JinLee, Yun-Sil
Ewha Authors
이윤실
SCOPUS Author ID
이윤실scopus
Issue Date
2015
Journal Title
ONCOTARGET
ISSN
1949-2553JCR Link
Citation
vol. 6, no. 30, pp. 29712 - 29724
Keywords
HSF1Ku70Ku86NHEJ Repaircellular carcinogenesis
Publisher
IMPACT JOURNALS LLC
Indexed
SCIE; SCOPUS WOS scopus
Abstract
A novel role for HSF1 as an inhibitor of non-homologous end joining (NHEJ) repair activity was identified. HSF1 interacted directly with both of the N-terminal sequences of the Ku70 and Ku86 proteins, which inhibited the endogenous heterodimeric interaction between Ku70 and Ku86. The blocking of the Ku70 and Ku86 interaction by HSF1 induced defective NHEJ repair activity and ultimately activated genomic instability after ionizing radiation (IR), which was similar to effects seen in Ku70 or Ku80 knockout cells. The binding activity between HSF1 and Ku70 or Ku86 was dependent on DNA damage response such as IR exposure, but not on the heat shock mediated transcriptional activation of HSF1. Moreover, the posttranslational modification such as phosphorylation, acetylation and sumoylation of HSF1 did not alter the binding activities of HSF1-Ku70 or HSF1-Ku86. Furthermore, the defect in DNA repair activity by HSF1 was observed regardless of p53 status. Rat mammary tumors derived using dimethylbenz(a)anthracence revealed that high levels of HSF1 expression which correlate with aggressive malignancy, interfered with the binding of Ku70-Ku80. This data suggests that HSF1 interacts with both Ku70 and Ku86 to induce defective NHEJ repair activity and genomic instability, which in turn suggests a novel mechanism of HSF1-mediated cellular carcinogenesis.
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약학대학 > 약학과 > Journal papers
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