Hélène Gaillard, Toni Ciudad, Andrés Aguilera, Ralf E. Wellinger
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引用次数: 0
摘要
活细胞的基因组不断受到 DNA 损伤的挑战,这些损伤干扰了转录和复制等细胞过程。多种机制协同作用,确保了 DNA 的充分修复、基因表达和基因组稳定性。大块 DNA 病变,如紫外线或 DNA 破坏剂 4-硝基氧化喹啉诱导的病变,是转录和复制的路障,因此对细胞新陈代谢构成重大威胁。当这些损伤位于活性基因的转录链上时,转录偶联核苷酸切除修复(TC-NER)会对其进行处理,这是一种尚未完全被理解的 NER 子途径。在这里,我们通过对酵母进行基因筛选,发现组蛋白变体H2A.Z是紫外线照射后保护转录和DNA完整性的重要成分。在缺乏 H2A.Z 的情况下,TC-NER 的修复功能严重受损,RNA 聚合酶 II 的清除率降低,导致双链断裂增加。因此,H2A.Z 是高效 TC-NER 的必要条件,在紫外线辐照后维持基因组稳定性方面发挥着重要作用。
Histone variant H2A.Z is needed for efficient transcription-coupled NER and genome integrity in UV challenged yeast cells
The genome of living cells is constantly challenged by DNA lesions that interfere with cellular processes such as transcription and replication. A manifold of mechanisms act in concert to ensure adequate DNA repair, gene expression, and genome stability. Bulky DNA lesions, such as those induced by UV light or the DNA-damaging agent 4-nitroquinoline oxide, act as transcriptional and replicational roadblocks and thus represent a major threat to cell metabolism. When located on the transcribed strand of active genes, these lesions are handled by transcription-coupled nucleotide excision repair (TC-NER), a yet incompletely understood NER sub-pathway. Here, using a genetic screen in the yeast Saccharomyces cerevisiae, we identified histone variant H2A.Z as an important component to safeguard transcription and DNA integrity following UV irradiation. In the absence of H2A.Z, repair by TC-NER is severely impaired and RNA polymerase II clearance reduced, leading to an increase in double-strand breaks. Thus, H2A.Z is needed for proficient TC-NER and plays a major role in the maintenance of genome stability upon UV irradiation.
期刊介绍:
PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill).
Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.