Possible involvement of LKB1-AMPK signaling in non-homologous end joining

A. Ui, H. Ogiwara, S. Nakajima, S. Kanno, R. Watanabe, M. Harata, H. Okayama, C. C. Harris, J. Yokota, A. Yasui, T. Kohno

研究成果: Article査読

23 被引用数 (Scopus)

抄録

LKB1/STK11 is a tumor suppressor gene responsible for Peutz-Jeghers syndrome, an inherited cancer disorder associated with genome instability. The LKB1 protein functions in the regulation of cell proliferation, polarization and differentiation. Here, we suggest a role of LKB1 in non-homologous end joining (NHEJ), a major DNA double-strand break (DSB) repair pathway. LKB1 localized to DNA ends upon the generation of micro-irradiation and I-SceI endonuclease-induced DSBs. LKB1 inactivation either by RNA interference or by kinase-dead mutation compromised NHEJ-mediated DNA repair by suppressing the accumulation of BRM, a catalytic subunit of the SWI/SNF complex, at DSB sites, which promotes the recruitment of an essential NHEJ factor, KU70. AMPK2, a major substrate of LKB1 and a histone H2B kinase, was recruited to DSBs in an LKB1-dependent manner. AMPK2 depletion and a mutation of H2B that disrupted the AMPK2 phoshorylation site impaired KU70 and BRM recruitment to DSB sites. LKB1 depletion induced the formation of chromosome breaks and radials. These results suggest that LKB1-AMPK signaling controls NHEJ and contributes to genome stability.

本文言語English
ページ(範囲)1640-1648
ページ数9
ジャーナルOncogene
33
13
DOI
出版ステータスPublished - 2014 3 27

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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