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人类 RECQL5 参与清除内源性 DNA 损伤。

Human RECQL5 participates in the removal of endogenous DNA damage.

机构信息

Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA.

出版信息

Mol Biol Cell. 2012 Nov;23(21):4273-85. doi: 10.1091/mbc.E12-02-0110. Epub 2012 Sep 12.

DOI:10.1091/mbc.E12-02-0110
PMID:22973052
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3484104/
Abstract

Human RECQL5 is a member of the RecQ helicase family, which maintains genome stability via participation in many DNA metabolic processes, including DNA repair. Human cells lacking RECQL5 display chromosomal instability. We find that cells depleted of RECQL5 are sensitive to oxidative stress, accumulate endogenous DNA damage, and increase the cellular poly(ADP-ribosyl)ate response. In contrast to the RECQ helicase family members WRN, BLM, and RECQL4, RECQL5 accumulates at laser-induced single-strand breaks in normal human cells. RECQL5 depletion affects the levels of PARP-1 and XRCC1, and our collective results suggest that RECQL5 modulates and/or directly participates in base excision repair of endogenous DNA damage, thereby promoting chromosome stability in normal human cells.

摘要

人类 RECQL5 是 RecQ 解旋酶家族的一员,通过参与包括 DNA 修复在内的多种 DNA 代谢过程来维持基因组稳定性。缺乏 RECQL5 的人类细胞表现出染色体不稳定性。我们发现,RECQL5 缺失的细胞对氧化应激敏感,会积累内源性 DNA 损伤,并增加细胞多聚(ADP-核糖基)化反应。与 RECQ 解旋酶家族成员 WRN、BLM 和 RECQL4 不同,RECQL5 在正常人类细胞中的激光诱导单链断裂处积累。RECQL5 缺失会影响 PARP-1 和 XRCC1 的水平,我们的综合结果表明,RECQL5 调节和/或直接参与内源性 DNA 损伤的碱基切除修复,从而促进正常人类细胞的染色体稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/8a59ee9220c1/4273fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/3837d98b4125/4273fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/f6ddcfb28cc8/4273fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/eacab02e6a5f/4273fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/c3572c8b116e/4273fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/fedaa7b35b87/4273fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/ce82f7700672/4273fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/8a59ee9220c1/4273fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/3837d98b4125/4273fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/f6ddcfb28cc8/4273fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/eacab02e6a5f/4273fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/c3572c8b116e/4273fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/fedaa7b35b87/4273fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/ce82f7700672/4273fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7e/3484104/8a59ee9220c1/4273fig7.jpg

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DNA Repair (Amst). 2012 Jul 1;11(7):624-35. doi: 10.1016/j.dnarep.2012.05.001. Epub 2012 May 24.
2
RECQ1 plays a distinct role in cellular response to oxidative DNA damage.RECQ1 在细胞对氧化 DNA 损伤的反应中发挥独特作用。
DNA Repair (Amst). 2012 Jun 1;11(6):537-49. doi: 10.1016/j.dnarep.2012.04.003. Epub 2012 Apr 26.
3
RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression.
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Nucleic Acids Res. 2018 Oct 12;46(18):9496-9509. doi: 10.1093/nar/gky727.
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Molecular-genetic profiling and high-throughput drug screening in NUT midline carcinoma-an aggressive and fatal disease.NUT中线癌的分子遗传学分析与高通量药物筛选——一种侵袭性致命疾病
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