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<p>DNA double-strand breaks (DSBs) are repaired mainly by non-homologous end-joining (NHEJ) and homologous recombination repair (HR) in mammalian cells. Recent studies highlight the importance of RNA in regulating these pathways and influencing pathway choice, particularly through the formation and resolution of DNA-RNA hybrids. Here, we show that DNA-RNA hybrids are formed at DSB sites in a PARP1- and poly (ADP-ribosyl)ation-dependent manner and are resolved by DHX9 dependent manner. The carboxyl-terminal RGG domain of DHX9 is necessary and sufficient for its recruitment and is required for efficient DNA end-resection. We further identify methylated arginine residues within this domain that are required for suppressing loading of the NHEJ-promoting factor 53BP1 to the DSB sites. Our findings highlight a central role of the RGG domain of DHX9 in DNA-RNA hybrid regulation and DSB repair pathway choice.</p>

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Dual roles of the DHX9 RGG domain in hybrid-dependent recruitment and suppression of 53BP1

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Yuina Tsuchiya,
  • Yudai Hiwatashi,
  • Hayaki Ikegame,
  • Saaya Matsuya,
  • Yurina Abe,
  • Ryotaro Nishi

摘要

DNA double-strand breaks (DSBs) are repaired mainly by non-homologous end-joining (NHEJ) and homologous recombination repair (HR) in mammalian cells. Recent studies highlight the importance of RNA in regulating these pathways and influencing pathway choice, particularly through the formation and resolution of DNA-RNA hybrids. Here, we show that DNA-RNA hybrids are formed at DSB sites in a PARP1- and poly (ADP-ribosyl)ation-dependent manner and are resolved by DHX9 dependent manner. The carboxyl-terminal RGG domain of DHX9 is necessary and sufficient for its recruitment and is required for efficient DNA end-resection. We further identify methylated arginine residues within this domain that are required for suppressing loading of the NHEJ-promoting factor 53BP1 to the DSB sites. Our findings highlight a central role of the RGG domain of DHX9 in DNA-RNA hybrid regulation and DSB repair pathway choice.