2025-09-08 東京大学
ピロリ菌が胃がんを起こすしくみ
ピロリ菌が作る制限酵素(DNAを切るハサミ)が,ヒトの胃の細胞に入りこみ,ゲノムDNAの特定の場所で塩基を切り出して,点変異と鎖切断によるゲノム再編を起こす。それらが胃がんの元になる。
<関連情報>
- https://www.k.u-tokyo.ac.jp/information/category/press/11739.html
- https://www.k.u-tokyo.ac.jp/information/upload/685e47f9d1e87e2a97e819da1e071915df46cf97.pdf
- https://academic.oup.com/pnasnexus/article/4/8/pgaf244/8222159
胃癌発生におけるヘリコバクター・ピロリ塩基切除制限酵素 Helicobacter pylori base-excision restriction enzyme in stomach carcinogenesis
Masaki Fukuyo, Noriko Takahashi, Katsuhiro Hanada, Ken Ishikawa, Česlovas Venclovas, Koji Yahara, Hideo Yonezawa, Takeshi Terabayashi, Yukako Katsura, Naoki Osada …
PNAS Nexus Published:05 August 2025
DOI:https://doi.org/10.1093/pnasnexus/pgaf244
Abstract
Many recent lines of evidence from the human microbiome and other fields indicate bacterial involvement in various types of cancer. Helicobacter pylori has been recognized as the major cause of stomach cancer (gastric cancer), but the mechanism by which it destabilizes the human genome to cause cancer remains unclear. Our recent studies have identified a unique family of toxic restriction enzymes that excise a base (A: adenine) from their recognition sequence (5′-GTAC). At the resulting abasic sites (5′-GT_C), its inherent endonuclease activity or that of a separate endonuclease may yield atypical strand breaks that resist repair by ligation. Here, we present evidence demonstrating involvement of its H. pylori member, HpPabI, in stomach carcinogenesis: (i) Association of intact HpPabI gene with gastric cancer in the global H. pylori Genome Project and the open genomes; (ii) Frequent mutations at A in 5′-GTAC in the gastric cancer genomes as well as in H. pylori genomes; (iii) Its induction of chromosomal double-strand breaks in infected human cells and of mutagenesis in bacterial test systems. In addition, its unique regions that interact with DNA exhibit signs of diversifying selection. Our further analysis revealed similar oncogenic bacterium–restriction–enzyme pairs for other types of cancer. These results set another stage for cancer research and medicine around oncogenic restriction enzymes.
