Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis.
Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis.
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DOI：
10.3390/genes12111779
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发表时间：
2021-11-09
期刊：
影响因子：
3.5
通讯作者：
Eckert KA
中科院分区：
文献类型：
--
作者：
Stein M;Eckert KA
基因组不稳定性是癌症的一个促成特征，对癌细胞进化至关重要。基因组不稳定性的热点，从小规模点突变到大规模结构变异，都与可能形成非B DNA结构的序列相关。G-四链体（G4）形成基序在癌症基因组中的结构变体端点处富集。慢性炎症是癌症发展的一种生理状态，氧化性DNA损伤通常被用来解释炎症如何促进基因组不稳定性。我们总结了G4和氧化应激重叠的地方，重点是DNA复制。鸟嘌呤具有低电离电位，使G4容易受到氧化损伤。对G4结构的影响取决于病变类型、位置和G4构象。偶尔，G4对复制型DNA聚合酶构成挑战，需要专门的DNA聚合酶来维持基因组稳定性。因此，慢性炎症给DNA聚合酶维持基因组稳定性带来了双重挑战：忠实的G4合成和绕过未修复的氧化损伤。炎症还伴随着可能影响诱变的整体转录组变化。几项研究表明，G4在癌症和炎症相关基因启动子中具有调节作用。我们讨论了炎症在多大程度上可以影响G4的基因调控，从而影响基因组的不稳定性，并强调了新研究的关键领域。
Genome instability is an enabling characteristic of cancer, essential for cancer cell evolution. Hotspots of genome instability, from small-scale point mutations to large-scale structural variants, are associated with sequences that potentially form non-B DNA structures. G-quadruplex (G4) forming motifs are enriched at structural variant endpoints in cancer genomes. Chronic inflammation is a physiological state underlying cancer development, and oxidative DNA damage is commonly invoked to explain how inflammation promotes genome instability. We summarize where G4s and oxidative stress overlap, with a focus on DNA replication. Guanine has low ionization potential, making G4s vulnerable to oxidative damage. Impacts to G4 structure are dependent upon lesion type, location, and G4 conformation. Occasionally, G4s pose a challenge to replicative DNA polymerases, requiring specialized DNA polymerases to maintain genome stability. Therefore, chronic inflammation creates a dual challenge for DNA polymerases to maintain genome stability: faithful G4 synthesis and bypassing unrepaired oxidative lesions. Inflammation is also accompanied by global transcriptome changes that may impact mutagenesis. Several studies suggest a regulatory role for G4s within cancer- and inflammatory-related gene promoters. We discuss the extent to which inflammation could influence gene regulation by G4s, thereby impacting genome instability, and highlight key areas for new investigation.
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影响因子：
14.9
作者：
Bacolla A;Zhu X;Chen H;Howells K;Cooper DN;Vasquez KM
通讯作者：
Vasquez KM
影响因子：
46.9
作者：
Chambers, Vicki S.;Marsico, Giovanni;Balasubramanian, Shankar
通讯作者：
Balasubramanian, Shankar
影响因子：
4.6
作者：
Bacolla, Albino;Wells, Robert D.
通讯作者：
Wells, Robert D.
G-四链体折叠和稳定性中的金属阳离子。
影响因子：
5.5
作者：
Bhattacharyya D;Mirihana Arachchilage G;Basu S
通讯作者：
Basu S
影响因子：
14.9
作者：
Du X;Gertz EM;Wojtowicz D;Zhabinskaya D;Levens D;Benham CJ;Schäffer AA;Przytycka TM
通讯作者：
Przytycka TM