Micronuclear collapse mechanisms in cancer

• 成果类型: Editorial Material
• 署名作者: Maddaluno, Marianna; Settembre, Carmine
• 署名单位: Fondazione Telethon; Telethon Institute of Genetics & Medicine (TIGEM); University of Naples Federico II
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10968
• DOI: 10.1126/science.adr7417
• 发表日期: 2024-08-30
• 页码: 930-931
• 关键词: nuclear-envelope; er

摘要

Errors in chromosome segregation during cell division (mitosis) can lead to chromosomal instability, a hallmark of human cancer. These mitotic errors give rise to the formation of micronuclei-small cytoplasmic structures that are spatially separated from the primary nucleus and contain lagging chromosomes or chromosome fragments. Unlike the primary nucleus of a cell, micronuclei frequently undergo irreparable rupture and collapse. This breakdown releases micronuclear DNA into the cytosol, causing DNA damage, chromosomal rearrangements, and genomic instability, thereby contributing to cancer progression. The rupture of micronuclei also activates a component of the innate immune system called the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway, leading to tumorrelated inflammation and metastasis (1). On pages 951 and 952 of this issue, Di Bona et al. (2) and Martin et al. (3), respectively, report the molecular underpinnings of micronuclear collapse.