气候变化领域集成服务门户(CCPortal): Clutch mechanism of chemomechanical coupling in a DNA resecting motor nuclease

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DOI	10.1073/pnas.2023955118
	Clutch mechanism of chemomechanical coupling in a DNA resecting motor nuclease
	Unciuleac M.-C.; Meir A.; Xue C.; Warren G.M.; Greene E.C.; Shuman S.
发表日期	2021
ISSN	00278424
卷号	118 期号:11
英文摘要	Mycobacterial AdnAB is a heterodimeric helicase.nuclease that initiates homologous recombination by resecting DNA double-strand breaks (DSBs). The N-terminal motor domain of the AdnB subunit hydrolyzes ATP to drive rapid and processive 3′ to 5′ translocation of AdnAB on the tracking DNA strand. ATP hydrolysis is mechanically productive when oscillating protein domain motions synchronized with the ATPase cycle propel the DNA tracking strand forward by a single-nucleotide step, in what is thought to entail a pawl-and-ratchet.like fashion. By gauging the effects of alanine mutations of the 16 amino acids at the AdnB.DNA interface on DNA-dependent ATP hydrolysis, DNA translocation, and DSB resection in ensemble and single-molecule assays, we gained key insights into which DNA contacts couple ATP hydrolysis to motor activity. The results implicate AdnB Trp325, which intercalates into the tracking strand and stacks on a nucleobase, as the singular essential constituent of the ratchet pawl, without which ATP hydrolysis on ssDNA is mechanically futile. Loss of Thr663 and Thr118 contacts with tracking strand phosphates and of His665 with a nucleobase drastically slows the AdnAB motor during DSB resection. Our findings for AdnAB prompt us to analogize its mechanism to that of an automobile clutch. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DNA repair; Helicase mechanism; Mycobacterium
语种	英语
scopus关键词	adenosine triphosphatase; adenosine triphosphate; AdnAB protein; alanine; double stranded DNA; nuclease; single stranded DNA; threonine; unclassified drug; amino terminal sequence; Article; chemical parameters; chemomechanical coupling; DNA strand; double stranded DNA break; hydrolysis; priority journal; protein DNA interaction; protein domain; protein subunit
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180279
作者单位	Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10065, United States; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, United States
推荐引用方式 GB/T 7714	Unciuleac M.-C.,Meir A.,Xue C.,et al. Clutch mechanism of chemomechanical coupling in a DNA resecting motor nuclease[J],2021,118(11).
APA	Unciuleac M.-C.,Meir A.,Xue C.,Warren G.M.,Greene E.C.,&Shuman S..(2021).Clutch mechanism of chemomechanical coupling in a DNA resecting motor nuclease.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA	Unciuleac M.-C.,et al."Clutch mechanism of chemomechanical coupling in a DNA resecting motor nuclease".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).