G-Quadruplex Helicase DHX36/G4R1 Engages Nuclear Lamina Proteins in Quiescent Breast Cancer Cells.

G-Quadruplex Helicase DHX36/G4R1 Engages Nuclear Lamina Proteins in Quiescent Breast Cancer Cells.
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DOI:
10.1021/acsomega.0c03723
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发表时间:
2020-09-29
期刊:
影响因子:
4.1
通讯作者:
Smaldino PJ
Smaldino PJ
中科院分区:
化学3区
文献类型:
--
作者:
Richardson AE;Zentz ZA;Chambers AE;Sandwith SN;Reisinger MA;Saunders DW;Tompkins JD;Riggs AD;Routh ED;Rubenstein EM;Smaldino MA;Vaughn JP;Haney RA;Smaldino PJ

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g -四联体(G4s)是一种在基因调控序列中富集的核酸结构。G4s控制着基本的细胞过程,包括复制、转录和翻译。原癌基因富含G4序列,而肿瘤抑制基因缺失,提示G4s在细胞存活和增殖中发挥作用。特殊解旋酶通过酶解绕活性参与g4介导的基因调控。其中一种酶DHX36/G4R1是主要的g4解旋酶,是g4 - dna和mrna的主要调节剂。g4分辨率促进促增殖基因的表达;因此,DHX36/G4R1促进细胞增殖。对于DHX36/G4R1本身在非分裂细胞中是如何调节的,我们知之甚少。我们假设当细胞从分裂状态过渡到静止状态时,DHX36/G4R1蛋白结合伙伴发生改变。我们发现DHX36/G4R1在静止条件下与一组不同的蛋白质共纯化,这可能代表了一种新的复合物,在细胞周期转变期间调节DHX36/G4R1,并对发育和癌症有影响。
G-quadruplexes (G4s) are nucleic acid structures found enriched within gene regulatory sequences. G4s control fundamental cellular processes, including replication, transcription, and translation. Proto-oncogenes are enriched with G4 sequences, while tumor-suppressor genes are depleted, suggesting roles for G4s in cell survival and proliferation. Specialized helicases participate in G4-mediated gene regulation via enzymatic unwinding activity. One such enzyme, DHX36/G4R1, is the major G4-helicase and is a master regulator of G4-DNAs and mRNAs. G4-resolution promotes the expression of proproliferative genes; as such, DHX36/G4R1 promotes cell proliferation. Little is known about how DHX36/G4R1 itself is regulated in nondividing cells. We hypothesized that DHX36/G4R1 protein binding partners are altered when a cell transitions from a dividing to a quiescent state. We found that DHX36/G4R1 co-purifies with a distinct set of proteins under quiescent conditions, which may represent a novel complex that regulates DHX36/G4R1 during cell cycle transitions and have implications for development and cancer.
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