非正规的MLL1活动调节了中心体相位分离和基因组稳定性
Liang Sha1, Zi Yang1, Sojin An2
1Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Nature cell biology
|November 9, 2023
概括
该MLL1/KMT2A酶通过一种新的非正规活性来调节基因组稳定性,甲基化玻利林以控制染色体乘客复合体 (CPC) 阶段分离并减少癌细胞生长.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 表观遗传失调,包括像MLL/KMT2这样的染色体调节器突变,在癌症中很常见.
- 虽然MLL1/KMT2A在H3K4甲基化中的作用已知,但其非正规功能在很大程度上未被描述.
研究的目的:
- 调查MLL1/KMT2A.未开发的非正规活动.
- 阐明MLL1/KMT2A在调节染色体乘客复合体 (CPC) 和基因组稳定中的作用.
主要方法:
- 对MLL1 SET域与玻里亚的共同晶体结构分析.
- 抑制MLL1活动和林K143.3突变的抑制.
- 测试CPC液-液相分离,紫外线激酶B活性,激光-微管附着物和姐妹染色体凝聚力.
主要成果:
- MLL1/KMT2A直接甲基化玻利K143,对于CPC相位分离至关重要.
- 这种甲基化中断会扰乱CPC相位分离,减少紫外线激酶B活性,并损害染色体分离和凝聚力.
- 这些缺陷导致肝细胞癌的染色体不稳定性增加和化,抑制瘤生长.
结论:
- MLL1/KMT2A具有非正规的酶活性,对于调节内心体液体凝结物至关重要.
- 这一功能对于保持基因组稳定性和抑制某些癌症瘤生长至关重要.
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