Genome-wide investigations on regulatory functions of RECQ1 helicase.

Genome-wide investigations on regulatory functions of RECQ1 helicase.
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DOI:
10.1016/j.ymeth.2022.02.010
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发表时间:
2022-08
期刊:
影响因子:
4.8
通讯作者:
Sharma, Sudha
Sharma, Sudha
中科院分区:
生物学3区
文献类型:
--
作者:
Debnath, Subrata;Lu, Xing;Lal, Ashish;Sharma, Sudha

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DNA解旋酶RECQ1(也称为RECQL或RECQL1)是与散发性乳腺癌患者的临床结果显著相关的候选乳腺癌易感基因。先前的研究表明,RECQ1通过调节多种核心细胞功能(包括DNA复制、DNA损伤反应和转录)来维持基因组稳定性。然而,目前尚不清楚这些功能中的哪些(如果有的话)是RECQ1与其抑制乳腺癌的作用相关的主要功能。我们在此描述了一种无偏倚的整合基因组学方法,该方法使我们能够发现RECQ1在促进雌激素受体α(ERα)表达和ER阳性乳腺癌细胞中特异性ERα靶基因表达方面的先前未知的调节作用。我们讨论了类似的实验策略在推进机制理解和阐明RECQ1和其他RecQ解旋酶在维持基因组稳定性和预防癌症方面的全基因组功能的具体新细节方面的潜在未来应用。
DNA helicase RECQ1 (also known as RECQL or RECQL1) is a candidate breast cancer susceptibility gene significantly correlated with clinical outcomes of sporadic breast cancer patients. Prior studies have suggested that RECQ1 maintains genomic stability by regulating a wide variety of core cellular functions including DNA replication, DNA damage response, and transcription. However, it is unclear which, if any, of these are the primary functions of RECQ1 as related to its role in suppressing breast cancer. We describe here an unbiased integrative genomics approach that enabled us to discover a previously unknown regulatory role of RECQ1 in promoting Estrogen Receptor alpha (ERα) expression and the expression of specific ERα target genes in ER positive breast cancer cells. We discuss potential future applications of similar experimental strategies in advancing the mechanistic understanding and elucidating specific new details of genome-wide functions of RECQ1 and other RecQ helicases in maintaining genomic stability and preventing cancer.
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