Unwinding forward and sliding back: an intermittent unwinding mode of the BLM helicase

Nucleic Acids Research
Shuang WangMing Li

Abstract

There are lines of evidence that the Bloom syndrome helicase, BLM, catalyzes regression of stalled replication forks and disrupts displacement loops (D-loops) formed during homologous recombination (HR). Here we constructed a forked DNA with a 3' single-stranded gap and a 5' double-stranded handle to partly mimic a stalled DNA fork and used magnetic tweezers to study BLM-catalyzed unwinding of the forked DNA. We have directly observed that the BLM helicase may slide on the opposite strand for some distance after duplex unwinding at different forces. For DNA construct with a long hairpin, progressive unwinding of the hairpin is frequently interrupted by strand switching and backward sliding of the enzyme. Quantitative study of the uninterrupted unwinding length (time) has revealed a two-state-transition mechanism for strand-switching during the unwinding process. Mutational studies revealed that the RQC domain plays an important role in stabilizing the helicase/DNA interaction during both DNA unwinding and backward sliding of BLM. Especially, Lys1125 in the RQC domain, a highly conserved amino acid among RecQ helicases, may be involved in the backward sliding activity. We have also directly observed the in vitro pathway that BLM...Continue Reading

References

Mar 29, 1996·Science·T R StrickV Croquette
Apr 12, 1996·Science·C E YuG D Schellenberg
Oct 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·B Essevaz-RouletF Heslot
Jan 10, 1998·The Journal of Biological Chemistry·J K KarowI D Hickson
Dec 16, 1997·Trends in Biochemical Sciences·V MorozovP Bork
Oct 9, 1998·The Journal of Biological Chemistry·H SunN Maizels
Dec 4, 1998·Science·H P LuX S Xie
Nov 5, 1999·Protein Expression and Purification·S F BerestenN A Ellis
Mar 15, 2000·Nature·M M CoxK J Marians
Apr 8, 2000·Current Opinion in Genetics & Development·K J Marians
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·J K KarowI D Hickson
Nov 23, 2000·Biochemistry·A J van BrabantW K Holloman
Jul 4, 2001·Nucleic Acids Research·P MohagheghI D Hickson
Nov 5, 2002·Nature Reviews. Molecular Cell Biology·Peter McGlynn, Robert G Lloyd
Jun 14, 2003·The Biochemical Journal·Csanád Z Bachrati, Ian D Hickson
Jun 24, 2003·Journal of Molecular Biology·Pavel JanscakThomas A Bickle
Oct 1, 2003·The EMBO Journal·Douglas A BernsteinJames L Keck
Oct 10, 2003·The Journal of Biological Chemistry·Cayetano von KobbeVilhelm A Bohr
Aug 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Bénédicte MichelVladimir Bidnenko
Oct 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Mitch McVeyJeff J Sekelsky
Jan 13, 2006·Nature Chemical Biology·Yuichi TaniguchiToshio Yanagida
Mar 15, 2006·Journal of Molecular Biology·Michael D HuberNancy Maizels
May 4, 2006·Nucleic Acids Research·Csanád Z BachratiIan D Hickson
Jun 13, 2006·The Journal of Biological Chemistry·Christine RalfLeonard Wu
Jul 3, 2007·Nature Structural & Molecular Biology·Sally L DaviesIan D Hickson
Dec 2, 2009·HFSP Journal·Alessandro Vindigni, Ian D Hickson
Mar 10, 2010·Nucleic Acids Research·Máté GyimesiMihály Kovács
Jul 20, 2010·Nucleic Acids Research·Young Mee Kim, Byong-Seok Choi
Aug 27, 2010·Journal of Biochemistry·Akiko SatoKen Kitano
Nov 13, 2010·Nucleic Acids Research·Nicholas LuzziettiRalf Seidel
Nov 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hamed Mirzaei, Kristina H Schmidt
Jun 19, 2013·Nature Communications·Daniel KlaueRalf Seidel
Nov 22, 2013·Scientific Reports·Sun-Yong KimKen Kitano
May 13, 2014·Acta Crystallographica. Section D, Biological Crystallography·Michael K SwanJay A Bertrand

❮ Previous
Next ❯

Citations

Nov 6, 2015·Critical Reviews in Biochemistry and Molecular Biology·Bo Sun, Michelle D Wang
Nov 21, 2015·Journal of Molecular Biology·Srinivas Somarowthu
Apr 14, 2016·Methods : a Companion to Methods in Enzymology·Sean M Carney, Michael A Trakselis
Apr 22, 2016·Nucleic Acids Research·Jing-Hua LiShuo-Xing Dou
Jul 13, 2016·Methods : a Companion to Methods in Enzymology·Felix E KemmerichRalf Seidel
Aug 9, 2016·Progress in Biophysics and Molecular Biology·Logan R Myler, Ilya J Finkelstein
Oct 6, 2017·Nucleic Acids Research·Ivona NecasováCtirad Hofr
Jun 9, 2019·The EMBO Journal·Kristina KasaciunaiteRalf Seidel
Apr 19, 2018·Nucleic Acids Research·Mina LeeSungchul Hohng
Jul 28, 2018·Nucleic Acids Research·Debjani BagchiVincent Croquette
Jul 4, 2019·The EMBO Journal·Kristina KasaciunaiteRalf Seidel
Jan 11, 2017·Proceedings of the National Academy of Sciences of the United States of America·Gábor M HaramiMihály Kovács
Dec 22, 2020·Nucleic Acids Research·Xu LiZhongbo Yu
Apr 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shuming ZhangHuidong Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
magnetic tweezers
fluorescence resonance energy transfer
FRET

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.