R-Loops in Genome Instability and Cancer.
R-Loops in Genome Instability and Cancer.
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R环在基因组不稳定性与癌症中的作用
DOI：
10.3390/cancers15204986
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发表时间：
2023-10-14
期刊：
影响因子：
5.2
通讯作者：
Zhang, Yanbin
中科院分区：
文献类型：
--
作者：
Li, Fang;Zafar, Alyan;Luo, Liang;Denning, Ariana Maria;Gu, Jun;Bennett, Ansley;Yuan, Fenghua;Zhang, Yanbin
关键词：
R环是由RNA-DNA杂交体和未配对的单链DNA（ssDNA）组成的三链结构，在细胞生理学和病理学条件中具有生物学意义。R环干扰DNA修复途径并激活癌基因，导致细胞增殖失调，基因组不稳定和癌症发展。R环在几种类型的癌细胞中积累，包括乳腺癌、卵巢癌、前列腺癌和肺癌。研究R环在癌症发展中的生物学作用可能有利于癌症的创新诊断和治疗方法。本文就R环在基因组不稳定性、DNA修复和致癌事件中的作用作一综述。R环是独特的三链核酸结构，其主要在RNA分子置换一条DNA链并与双链DNA分子中的互补DNA链退火时形成。R环形成可以在自然过程中发生，例如转录，其中新生RNA分子保持与模板DNA链杂交，而非模板DNA链被置换。然而，R环也可能由于许多非自然过程而出现，包括DNA损伤，RNA降解途径的失调和RNA加工中的缺陷。尽管它们在整个基因组中普遍存在，但R环主要存在于活跃转录的基因区域，使R环能够发挥看似有争议的作用。一方面，R环的病理性积累导致基因组不稳定性，这是癌症发展的标志，在肿瘤发生、癌症进展和治疗抗性中起作用。另一方面，R环在调控基因表达、染色质组织、类别转换重组、线粒体DNA复制和DNA修复等重要过程中起着关键作用。在这篇综述中，我们总结了与R环的形成、抑制和去除相关的发现及其对基因组不稳定性、DNA修复和致癌事件的影响。我们还讨论了通过靶向病理性R环的治疗机会。
R-loops are three-stranded structures consisting of an RNA–DNA hybrid and an unpaired single-stranded DNA (ssDNA), with biological implications in cellular physiology and pathological conditions. R-loops interfere with DNA repair pathways and activate oncogenes, leading to dysregulated cell proliferation, genome instability, and cancer development. R-loops accumulate in several types of cancer cells, including breast, ovarian, prostate, and lung cancer. Studying the biological roles of R-loops in cancer development is potentially beneficial for innovative diagnostic and treatment approaches for cancer. In this review, we focus on recent advances in R-loops’ roles in genome instability, DNA repair, and oncogenic events. R-loops are unique, three-stranded nucleic acid structures that primarily form when an RNA molecule displaces one DNA strand and anneals to the complementary DNA strand in a double-stranded DNA molecule. R-loop formation can occur during natural processes, such as transcription, in which the nascent RNA molecule remains hybridized with the template DNA strand, while the non-template DNA strand is displaced. However, R-loops can also arise due to many non-natural processes, including DNA damage, dysregulation of RNA degradation pathways, and defects in RNA processing. Despite their prevalence throughout the whole genome, R-loops are predominantly found in actively transcribed gene regions, enabling R-loops to serve seemingly controversial roles. On one hand, the pathological accumulation of R-loops contributes to genome instability, a hallmark of cancer development that plays a role in tumorigenesis, cancer progression, and therapeutic resistance. On the other hand, R-loops play critical roles in regulating essential processes, such as gene expression, chromatin organization, class-switch recombination, mitochondrial DNA replication, and DNA repair. In this review, we summarize discoveries related to the formation, suppression, and removal of R-loops and their influence on genome instability, DNA repair, and oncogenic events. We have also discussed therapeutical opportunities by targeting pathological R-loops.
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影响因子：
14.9
作者：
Block-Schmidt AS;Dukowic-Schulze S;Wanieck K;Reidt W;Puchta H
通讯作者：
Puchta H
影响因子：
16.6
作者：
Arora, Rajika;Lee, Yongwoo;Wischnewski, Harry;Brun, Catherine M.;Schwarz, Tobias;Azzalin, Claus M.
通讯作者：
Azzalin, Claus M.
影响因子：
64.5
作者：
Barlow JH;Faryabi RB;Callén E;Wong N;Malhowski A;Chen HT;Gutierrez-Cruz G;Sun HW;McKinnon P;Wright G;Casellas R;Robbiani DF;Staudt L;Fernandez-Capetillo O;Nussenzweig A
通讯作者：
Nussenzweig A
DOI：
10.1038/nrm.2017.27
发表时间：
2017-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Baralle FE;Giudice J
通讯作者：
Giudice J
影响因子：
56.9
作者：
Azzalin, Claus M.;Reichenbach, Patrick;Lingner, Joachim
通讯作者：
Lingner, Joachim