TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends

Akimitsu Konishi; Takashi Izumi; Shigeomi Shimizu

doi:10.1074/jbc.M116.719021

TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends*

From the ^‡Department of Pathological Cell Biology and
^§Medical Top Track Program, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan,
the ^¶Department of Biochemistry, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan, and
the ^‖Laboratory of Cell Biology and Genetics, The Rockefeller University, New York, New York 10065

↵1 To whom correspondence should be addressed: Dept. of Biochemistry, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan. Tel.: 81-27-220-7941; Fax: 81-27-220-7948; E-mail: akimitsukonishi{at}gunma-u.ac.jp.

Abstract

Mammalian chromosome ends are protected by a specialized nucleoprotein complex called telomeres. Both shelterin, a telomere-specific multi-protein complex, and higher order telomeric chromatin structures combine to stabilize the chromosome ends. Here, we showed that TRF2, a component of shelterin, binds to core histones to protect chromosome ends from inappropriate DNA damage response and loss of telomeric DNA. The N-terminal Gly/Arg-rich domain (GAR domain) of TRF2 directly binds to the globular domain of core histones. The conserved arginine residues in the GAR domain of TRF2 are required for this interaction. A TRF2 mutant with these arginine residues substituted by alanine lost the ability to protect telomeres and induced rapid telomere shortening caused by the cleavage of a loop structure of the telomeric chromatin. These findings showed a previously unnoticed interaction between the shelterin complex and nucleosomal histones to stabilize the chromosome ends.

Footnotes

↵* This work was supported by the Program for Improvement of Research Environment for Young Researchers from Special Coordination Funds for Promoting Science and Technology (SCF) commissioned by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. The authors declare that they have no conflicts of interest with the contents of this article.