Correction to Differential Stabilities and Sequence-Dependent Base Pair Opening Dynamics of Watson–Crick Base Pairs with 5-Hydroxymethylcytosine, 5-Formylcytosine, or 5-Carboxylcytosine

Abstract Mismatch repair is a highly conserved cellular pathway responsible for repairing mismatched dsDNA. Errors are detected by the MutS enzyme, which most likely senses altered mechanical property of damaged dsDNA rather than a specific molecular pattern. While the curved shape of dsDNA in crystallographic MutS/DNA structures suggests the role of DNA bending, the theoretical support is not fully convincing. Here, we present a computational study focused on a base-pair opening into the minor groove, a specific base-pair motion observed upon interaction with MutS. Propensities for the opening were evaluated in terms of two base-pair parameters: Opening and Shear. We tested all possible base pairs in anti/anti, anti/syn and syn/anti orientations and found clear discrimination between mismatches and canonical base-pairs only for the opening into the minor groove. Besides, the discrimination gap was also confirmed in hotspot and coldspot sequences, indicating that the opening could play a more significant role in the mismatch recognition than previously recognized. Our findings can be helpful for a better understanding of sequence-dependent mutability. Further, detailed structural characterization of mismatches can serve for designing anti-cancer drugs targeting mismatched base pairs.

Download Full-text

Asymmetric base-pair opening drives helicase unwinding dynamics

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1901086116 ◽

2019 ◽

Vol 116 (45) ◽

pp. 22471-22477 ◽

Cited By ~ 4

Author(s):

Francesco Colizzi ◽

Cibran Perez-Gonzalez ◽

Remi Fritzen ◽

Yaakov Levy ◽

Malcolm F. White ◽

...

Keyword(s):

Base Pair ◽

Double Helix ◽

The Other ◽

Base Pairs ◽

Dna Helicases ◽

Cellular Processes ◽

Dna Base ◽

Dna Base Pairs ◽

Opening And Closing ◽

Base Pair Opening

The opening of a Watson–Crick double helix is required for crucial cellular processes, including replication, repair, and transcription. It has long been assumed that RNA or DNA base pairs are broken by the concerted symmetric movement of complementary nucleobases. By analyzing thousands of base-pair opening and closing events from molecular simulations, here, we uncover a systematic stepwise process driven by the asymmetric flipping-out probability of paired nucleobases. We demonstrate experimentally that such asymmetry strongly biases the unwinding efficiency of DNA helicases toward substrates that bear highly dynamic nucleobases, such as pyrimidines, on the displaced strand. Duplex substrates with identical thermodynamic stability are thus shown to be more easily unwound from one side than the other, in a quantifiable and predictable manner. Our results indicate a possible layer of gene regulation coded in the direction-dependent unwindability of the double helix.

Download Full-text

High Base Pair Opening Rates in Tracts of GC Base Pairs

Journal of Biological Chemistry ◽

10.1074/jbc.274.11.6957 ◽

1999 ◽

Vol 274 (11) ◽

pp. 6957-6962 ◽

Cited By ~ 84

Author(s):

Utz Dornberger ◽

Mikael Leijon ◽

Hartmut Fritzsche

Keyword(s):

Base Pair ◽

Base Pairs ◽

High Base ◽

Base Pair Opening

Download Full-text

Sequence-Dependent T:G Base Pair Opening in DNA Double Helix Bound by Cren7, a Chromatin Protein Conserved among Crenarchaea

PLoS ONE ◽

10.1371/journal.pone.0163361 ◽

2016 ◽

Vol 11 (9) ◽

pp. e0163361 ◽

Cited By ~ 1

Author(s):

Lei Tian ◽

Zhenfeng Zhang ◽

Hanqian Wang ◽

Mohan Zhao ◽

Yuhui Dong ◽

...

Keyword(s):

Base Pair ◽

Double Helix ◽

Chromatin Protein ◽

Sequence Dependent ◽

Dna Double Helix ◽

Base Pair Opening

Download Full-text

Detection of the Glanzmann's Thrombasthenia Mutations in Arab and Iraqi-Jewish Patients by Polymerase Chain Reaction and Restriction Analysis of Blood or Urine Samples

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646446 ◽

1991 ◽

Vol 66 (04) ◽

pp. 500-504 ◽

Cited By ~ 28

Author(s):

H Peretz ◽

U Seligsohn ◽

E Zwang ◽

B S Coller ◽

P J Newman

Keyword(s):

Polymerase Chain Reaction ◽

Base Pair ◽

Restriction Analysis ◽

Urine Samples ◽

Chain Reaction ◽

Base Pairs ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia ◽

Base Pair Deletion ◽

Polymerase Chain

SummarySevere Glanzmann's thrombasthenia is relatively frequent in Iraqi-Jews and Arabs residing in Israel. We have recently described the mutations responsible for the disease in Iraqi-Jews – an 11 base pair deletion in exon 12 of the glycoprotein IIIa gene, and in Arabs – a 13 base pair deletion at the AG acceptor splice site of exon 4 on the glycoprotein IIb gene. In this communication we show that the Iraqi-Jewish mutation can be identified directly by polymerase chain reaction and gel electrophoresis. With specially designed oligonucleotide primers encompassing the mutation site, an 80 base pair segment amplified in healthy controls was clearly distinguished from the 69 base pair segment produced in patients. Patients from 11 unrelated Iraqi-Jewish families had the same mutation. The Arab mutation was identified by first amplifying a DNA segment consisting of 312 base pairs in controls and of 299 base pairs in patients, and then digestion by a restriction enzyme Stu-1, which recognizes a site that is absent in the mutant gene. In controls the 312 bp segment was digested into 235 and 77 bp fragments, while in patients there was no change in the size of the amplified 299 bp segment. The mutation was found in patients from 3 out of 5 unrelated Arab families. Both Iraqi-Jewish and Arab mutations were detectable in DNA extracted from blood and urine samples. The described simple methods of identifying the mutations should be useful for detection of the numerous potential carriers among the affected kindreds and for prenatal diagnosis using DNA extracted from chorionic villi samples.

Download Full-text

Base-Pair Opening Dynamics Study of Fluoride Riboswitch in the Bacillus cereus CrcB Gene

International Journal of Molecular Sciences ◽

10.3390/ijms22063234 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3234

Author(s):

Juhyun Lee ◽

Si-Eun Sung ◽

Janghyun Lee ◽

Jin Young Kang ◽

Joon-Hwa Lee ◽

...

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Nmr Spectroscopy ◽

Bacillus Cereus ◽

Base Pair ◽

Noncoding Rna ◽

Hydrogen Exchange ◽

Magnesium Ion ◽

Fluoride Ion ◽

Base Pair Opening

Riboswitches are segments of noncoding RNA that bind with metabolites, resulting in a change in gene expression. To understand the molecular mechanism of gene regulation in a fluoride riboswitch, a base-pair opening dynamics study was performed with and without ligands using the Bacillus cereus fluoride riboswitch. We demonstrate that the structural stability of the fluoride riboswitch is caused by two steps depending on ligands. Upon binding of a magnesium ion, significant changes in a conformation of the riboswitch occur, resulting in the greatest increase in their stability and changes in dynamics by a fluoride ion. Examining hydrogen exchange dynamics through NMR spectroscopy, we reveal that the stabilization of the U45·A37 base-pair due to the binding of the fluoride ion, by changing the dynamics while maintaining the structure, results in transcription regulation. Our results demonstrate that the opening dynamics and stabilities of a fluoride riboswitch in different ion states are essential for the genetic switching mechanism.

Download Full-text

The structure of recA protein-DNA filaments. 2 recA protein monomers unwind 17 base pairs of DNA by 11.5 degrees/base pair in the presence of adenosine 5'-O-(3-thiotriphosphate).

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)44222-0 ◽

1983 ◽

Vol 258 (20) ◽

pp. 12624-12631 ◽

Cited By ~ 6

Author(s):

S Chrysogelos ◽

J C Register ◽

J Griffith

Keyword(s):

Base Pair ◽

Reca Protein ◽

Base Pairs

Download Full-text

Base Pair Opening in a Deoxynucleotide Duplex Containing a cis-syn Thymine Cyclobutane Dimer Lesion

Biochemistry ◽

10.1021/bi401312r ◽

2013 ◽

Vol 52 (51) ◽

pp. 9275-9285 ◽

Cited By ~ 5

Author(s):

Belinda B. Wenke ◽

Leah N. Huiting ◽

Elisa B. Frankel ◽

Benjamin F. Lane ◽

Megan E. Núñez

Keyword(s):

Base Pair ◽

Cyclobutane Dimer ◽

Base Pair Opening

Download Full-text

Repair of heteroduplex plasmid DNA after transformation into Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.6.10.3401-3409.1986 ◽

1986 ◽

Vol 6 (10) ◽

pp. 3401-3409

Author(s):

D K Bishop ◽

R D Kolodner

Keyword(s):

Saccharomyces Cerevisiae ◽

Plasmid Dna ◽

Base Pair ◽

Base Pairs ◽

Plasmid Dnas ◽

Repair Efficiency ◽

Single Insertion ◽

Base Pair Insertion

Purified heteroduplex plasmid DNAs containing 8- or 12-base-pair insertion mismatches or AC or CT substitution mismatches were used to transform Saccharomyces cerevisiae. Two insertion mismatches, separated by 943 base pairs, were repaired independently of each other at least 55% of the time. This suggested that repair tracts were frequently shorter than 1 kilobase. The two insertion mismatches were repaired with different efficiencies. Comparison of the repair efficiency of one mismatched site with or without an adjacent mismatch suggests that mismatches promote their own repair and can influence the repair of neighboring mismatches. When two different plasmids containing single-insertion mismatches were transformed into S. cerevisiae cells, a slight preference towards insertion was detected among repair products of one of the two plasmids, while no repair preference was detected among transformants with the second plasmid.

Download Full-text