Department of Pathology & Immunology, Division of Laboratory and Genomic Medicine, Center for Genome Integrity, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Pathology & Immunology, Division of Laboratory and Genomic Medicine, Center for Genome Integrity, Washington University School of Medicine, St. Louis, MO 63110, USA.
DNA Repair (Amst). 2023 Nov;131:103564. doi: 10.1016/j.dnarep.2023.103564. Epub 2023 Sep 9.
The central dogma of molecular biology posits that genetic information flows unidirectionally, from DNA, to RNA, and finally to protein. However, this directionality is broken in some cases, such as reverse transcription where RNA is converted to DNA by retroviruses and certain transposable elements. Our genomes have evolved and adapted to the presence of reverse transcription. Similarly, our genome is continuously maintained by several repair pathways to reverse damage due to various endogenous and exogenous sources. More recently, evidence has revealed that RNA, while in certain contexts may be detrimental for genome stability, is involved in promoting certain types of DNA repair. Depending on the pathway in question, the size of these DNA repair-associated RNAs range from one or a few ribonucleotides to long fragments of RNA. Moreover, RNA is highly modified, and RNA modifications have been revealed to be functionally associated with specific DNA repair pathways. In this review, we highlight aspects of this unexpected layer of genomic maintenance, demonstrating how RNA may influence DNA integrity.
分子生物学的中心法则假定遗传信息是单向流动的,从 DNA 到 RNA,最后到蛋白质。然而,在某些情况下,这种方向性被打破了,例如逆转录,在逆转录过程中,逆转录病毒和某些转座元件将 RNA 转化为 DNA。我们的基因组已经进化并适应了逆转录的存在。同样,我们的基因组通过几种修复途径来持续维持,以逆转由于各种内源性和外源性来源造成的损伤。最近的证据表明,在某些情况下,RNA 可能对基因组稳定性有害,但它参与促进某些类型的 DNA 修复。根据所涉及的途径,这些与 DNA 修复相关的 RNA 的大小从一个或几个核苷酸到长片段的 RNA 不等。此外,RNA 高度修饰,并且已经揭示 RNA 修饰与特定的 DNA 修复途径具有功能相关性。在这篇综述中,我们强调了基因组维持的这一意想不到的层面的各个方面,展示了 RNA 如何影响 DNA 完整性。