The duplication of the eukaryotic genome is an intricate process that has to be tightly safe-guarded. One of the most frequently occurring errors during DNA synthesis is the mis-insertion of a ribonucleotide instead of a deoxyribonucleotide. Ribonucleotide excision repair (RER) is initiated by RNase H2 and results in error-free removal of such mis-incorporated ribonucleotides. If left unrepaired, DNA-embedded ribonucleotides result in a variety of alterations within chromosomal DNA, which ultimately lead to genome instability. Here, we review how genomic ribonucleotides lead to chromosomal aberrations and discuss how the tight regulation of RER timing may be important for preventing unwanted DNA damage. We describe the structural impact of unrepaired ribonucleotides on DNA and chromatin and comment on the potential consequences for cellular fitness. In the context of the molecular mechanisms associated with faulty RER, we have placed an emphasis on how and why increased levels of genomic ribonucleotides are associated with severe autoimmune syndromes, neuropathology, and cancer. In addition, we discuss therapeutic directions that could be followed for pathologies associated with defective removal of ribonucleotides from double-stranded DNA.

中文翻译：

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错误的真核核糖核苷酸切除修复的分子和生理后果。

真核基因组的复制是一个复杂的过程，必须受到严格保护。DNA 合成过程中最常发生的错误之一是错误插入核糖核苷酸而不是脱氧核糖核苷酸。核糖核苷酸切除修复 (RER) 由 RNase H2 启动，可无差错地去除此类错误掺入的核糖核苷酸。如果不进行修复，DNA 嵌入的核糖核苷酸会导致染色体 DNA 内发生多种改变，最终导致基因组不稳定。在这里，我们回顾了基因组核糖核苷酸如何导致染色体畸变，并讨论了 RER 时序的严格调控对于防止不必要的 DNA 损伤可能很重要。我们描述了未修复的核糖核苷酸对 DNA 和染色质的结构影响，并评论了对细胞健康的潜在后果。在与 RER 缺陷相关的分子机制背景下，我们重点关注基因组核糖核苷酸水平增加如何以及为何与严重自身免疫综合征、神经病理学和癌症相关。此外，我们还讨论了与双链 DNA 中核糖核苷酸去除缺陷相关的病理学可遵循的治疗方向。