Feng Yuchen, Klionsky Daniel J
a Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan , Ann Arbor , MI , USA.
Autophagy. 2017 Jun 3;13(6):995-996. doi: 10.1080/15548627.2017.1317427.
Macroautophagy/autophagy is primarily a degradative pathway that clears malfunctioning cellular components in response to various types of stress. Recent studies have indicated that autophagy also plays an important role in maintaining genome stability. Loss of autophagy is associated with increased damage to DNA, inappropriate amplification of genomic regions and abnormal chromosome number. In a recent paper by Wang et al. the authors uncover a mechanism through which autophagy regulates the ubiquitination of chromatin. In particular, the autophagy receptor and substrate SQSTM1/p62 inhibits the E3 ligase RNF168-dependent ubiquitination of histone in response to DNA double-strand breaks. Dysregulation of this process leads to a reduced ability to repair DNA and a corresponding increase in the sensitivity of cells to radiation-induced damage.
巨自噬/自噬主要是一种降解途径，可清除因各种应激而功能失调的细胞成分。最近的研究表明，自噬在维持基因组稳定性方面也起着重要作用。自噬缺失与DNA损伤增加、基因组区域的不适当扩增以及染色体数目异常有关。在Wang等人最近发表的一篇论文中，作者揭示了一种自噬调节染色质泛素化的机制。具体而言，自噬受体及底物SQSTM1/p62在DNA双链断裂时可抑制E3连接酶RNF168介导的组蛋白泛素化。该过程的失调会导致DNA修复能力下降，相应地细胞对辐射诱导损伤的敏感性增加。
