scholarly journals Fork Stalling and Template Switching in the Context of a ‘Rearrangement Factory’: FoSTeS Can Mediate Higher Order Chromatin Rearrangements

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Saeed Taheri
Keyword(s):  
Higher Order ◽  
Template Switching ◽  
Fork Stalling

scholarly journals Repriming DNA synthesis: an intrinsic restart pathway that maintains efficient genome replication

2021 ◽  
Author(s):  
Lewis J Bainbridge ◽  
Rebecca Teague ◽  
Aidan J Doherty
Keyword(s):  
Dna Synthesis ◽  
Template Switching ◽  
Genome Replication ◽  
Diverse Range ◽  
General Role ◽  
Past Half Century ◽  
Dna Strands ◽  
Domains Of Life ◽  
Leading Strand ◽  
Fork Stalling

Abstract To bypass a diverse range of fork stalling impediments encountered during genome replication, cells possess a variety of DNA damage tolerance (DDT) mechanisms including translesion synthesis, template switching, and fork reversal. These pathways function to bypass obstacles and allow efficient DNA synthesis to be maintained. In addition, lagging strand obstacles can also be circumvented by downstream priming during Okazaki fragment generation, leaving gaps to be filled post-replication. Whether repriming occurs on the leading strand has been intensely debated over the past half-century. Early studies indicated that both DNA strands were synthesised discontinuously. Although later studies suggested that leading strand synthesis was continuous, leading to the preferred semi-discontinuous replication model. However, more recently it has been established that replicative primases can perform leading strand repriming in prokaryotes. An analogous fork restart mechanism has also been identified in most eukaryotes, which possess a specialist primase called PrimPol that conducts repriming downstream of stalling lesions and structures. PrimPol also plays a more general role in maintaining efficient fork progression. Here, we review and discuss the historical evidence and recent discoveries that substantiate repriming as an intrinsic replication restart pathway for maintaining efficient genome duplication across all domains of life.

scholarly journals DNA damage tolerance in stem cells, ageing, mutagenesis, disease and cancer therapy

2019 ◽  
Vol 47 (14) ◽  
pp. 7163-7181 ◽  
Author(s):  
Bas Pilzecker ◽  
Olimpia Alessandra Buoninfante ◽  
Heinz Jacobs
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Damage Tolerance ◽  
Essential Feature ◽  
Dna Lesions ◽  
Template Switching ◽  
Dna Damage Tolerance ◽  
Response Network ◽  
Damage Response ◽  
Fork Stalling

AbstractThe DNA damage response network guards the stability of the genome from a plethora of exogenous and endogenous insults. An essential feature of the DNA damage response network is its capacity to tolerate DNA damage and structural impediments during DNA synthesis. This capacity, referred to as DNA damage tolerance (DDT), contributes to replication fork progression and stability in the presence of blocking structures or DNA lesions. Defective DDT can lead to a prolonged fork arrest and eventually cumulate in a fork collapse that involves the formation of DNA double strand breaks. Four principal modes of DDT have been distinguished: translesion synthesis, fork reversal, template switching and repriming. All DDT modes warrant continuation of replication through bypassing the fork stalling impediment or repriming downstream of the impediment in combination with filling of the single-stranded DNA gaps. In this way, DDT prevents secondary DNA damage and critically contributes to genome stability and cellular fitness. DDT plays a key role in mutagenesis, stem cell maintenance, ageing and the prevention of cancer. This review provides an overview of the role of DDT in these aspects.

scholarly journals Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching

2009 ◽  
Vol 18 (12) ◽  
pp. 2188-2203 ◽  
Author(s):  
Claudia M.B. Carvalho ◽  
Feng Zhang ◽  
Pengfei Liu ◽  
Ankita Patel ◽  
Trilochan Sahoo ◽  
...  
Keyword(s):  
Template Switching ◽  
Fork Stalling

Gene amplification: mechanisms and involvement in cancer

2013 ◽  
Vol 4 (6) ◽  
pp. 567-582 ◽  
Author(s):  
Atsuka Matsui ◽  
Tatsuya Ihara ◽  
Hiraku Suda ◽  
Hirofumi Mikami ◽  
Kentaro Semba
Keyword(s):  
Drosophila Melanogaster ◽  
Gene Amplification ◽  
Dihydrofolate Reductase ◽  
Mammalian Cells ◽  
Replication Fork ◽  
Template Switching ◽  
Rolling Circle Replication ◽  
Rolling Circle ◽  
Reductase Gene ◽  
Fork Stalling

AbstractGene amplification was recognized as a physiological process during the development of Drosophila melanogaster. Intriguingly, mammalian cells use this mechanism to overexpress particular genes for survival under stress, such as during exposure to cytotoxic drugs. One well-known example is the amplification of the dihydrofolate reductase gene observed in methotrexate-resistant cells. Four models have been proposed for the generation of amplifications: extrareplication and recombination, the breakage-fusion-bridge cycle, double rolling-circle replication, and replication fork stalling and template switching. Gene amplification is a typical genetic alteration in cancer, and historically many oncogenes have been identified in the amplified regions. In this regard, novel cancer-associated genes may remain to be identified in the amplified regions. Recent comprehensive approaches have further revealed that co-amplified genes also contribute to tumorigenesis in concert with known oncogenes in the same amplicons. Considering that cancer develops through the alteration of multiple genes, gene amplification is an effective acceleration machinery to promote tumorigenesis. Identification of cancer-associated genes could provide novel and effective therapeutic targets.

Identification and characterisation of a novel aberrant pattern of intron 1 inversion with concomitant large insertion and deletion within the F8 gene

2014 ◽  
Vol 112 (08) ◽  
pp. 264-270 ◽  
Author(s):  
Guoling You ◽  
Kun Chi ◽  
Yeling Lu ◽  
Qiulan Ding ◽  
Jing Dai ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Copy Number Variations ◽  
Genomic Rearrangement ◽  
Causative Mutation ◽  
Template Switching ◽  
Insertion And Deletion ◽  
Complex Genomic Rearrangement ◽  
Intron 1 ◽  
Fork Stalling ◽  
Intron 1 Inversion

SummaryIntron 1 inversion (Inv1) is a recurrent causative mutation of haemophilia A (HA) and is responsible for 1–5% of severe HA. Inv1 occurs as a result of intra-chromosomal homologous recombination between int1h-1 within intron 1 and int1h-2 located in approximately 125 kb telomeric to the F8 gene. In this report, we presented a previously undescribed aberrant type of Inv1 with complex genomic rearrangement in a pedigree with severe HA. The breakpoints of the rearrangement were identified by the genome walking technique; copy number variations (CNVs) of the F8 gene and X chromosome were detected by AccuCopy technique, Affymetrix CytoScan HD CNV assay and quantitative PCR (qPCR); the F8 transcripts related to the aberrant Inv1 were analysed by reverse transcription PCR (RT-PCR). We have characterised the exact breakpoints of the complex rearrangement, and determined the location and size of the insertion and deletion. The rearrangements can be summarised as an aberrant pattern of Inv1 with a deletion of 2.56 kb and a duplication of 227.3 kb inserted in the rejoining junction within the F8 gene. Our results suggested that this complex genomic rearrangement was generated by two distinct repair mechanisms of fork stalling and template switching/microhomology-mediated break-induced replication (FoSTeS/MMBIR) and nonallelic homologous recombination (NAHR).

Dual systems for all: Higher-order, role-based relational reasoning as a uniquely derived feature of human cognition

2019 ◽  
Vol 42 ◽  
Author(s):  
Daniel J. Povinelli ◽  
Gabrielle C. Glorioso ◽  
Shannon L. Kuznar ◽  
Mateja Pavlic
Keyword(s):  
Temporal Reasoning ◽  
Higher Order ◽  
Important Case ◽  
Human Cognition ◽  
Relational Reasoning ◽  
Dual Systems ◽  
First Order ◽  
Reasoning System ◽  
Role Based

Abstract Hoerl and McCormack demonstrate that although animals possess a sophisticated temporal updating system, there is no evidence that they also possess a temporal reasoning system. This important case study is directly related to the broader claim that although animals are manifestly capable of first-order (perceptually-based) relational reasoning, they lack the capacity for higher-order, role-based relational reasoning. We argue this distinction applies to all domains of cognition.

Quantitative EPMA of nitrogen : A tricky element in the electron-probe microanalyzer

1992 ◽  
Vol 50 (2) ◽  
pp. 1622-1623
Author(s):  
G.F. Bastin ◽  
H.J.M. Heijligers
Keyword(s):  
Background Subtraction ◽  
Electron Probe ◽  
Detection System ◽  
Higher Order ◽  
Light Elements ◽  
Strong Suppression ◽  
Electron Probe Microanalyzer ◽  
Quantitative Epma ◽  
Peak Count ◽  
Lead Stearate

Among the ultra-light elements B, C, N, and O nitrogen is the most difficult element to deal with in the electron probe microanalyzer. This is mainly caused by the severe absorption that N-Kα radiation suffers in carbon which is abundantly present in the detection system (lead-stearate crystal, carbonaceous counter window). As a result the peak-to-background ratios for N-Kα measured with a conventional lead-stearate crystal can attain values well below unity in many binary nitrides . An additional complication can be caused by the presence of interfering higher-order reflections from the metal partner in the nitride specimen; notorious examples are elements such as Zr and Nb. In nitrides containing these elements is is virtually impossible to carry out an accurate background subtraction which becomes increasingly important with lower and lower peak-to-background ratios. The use of a synthetic multilayer crystal such as W/Si (2d-spacing 59.8 Å) can bring significant improvements in terms of both higher peak count rates as well as a strong suppression of higher-order reflections.

Effects of Higher-Order Laue Zone reflections on structure images

1993 ◽  
Vol 51 ◽  
pp. 450-451
Author(s):  
H. S. Kim ◽  
S. S. Sheinin
Keyword(s):  
Wave Vector ◽  
Theoretical Calculations ◽  
Reciprocal Lattice ◽  
Image Plane ◽  
Bloch Wave ◽  
Dynamical Theory ◽  
Higher Order ◽  
Lattice Image ◽  
Lattice Vector ◽  
Image Position

The importance of image simulation in interpreting experimental lattice images is well established. Normally, in carrying out the required theoretical calculations, only zero order Laue zone reflections are taken into account. In this paper we assess the conditions for which this procedure is valid and indicate circumstances in which higher order Laue zone reflections may be important. Our work is based on an analysis of the requirements for obtaining structure images i.e. images directly related to the projected potential. In the considerations to follow, the Bloch wave formulation of the dynamical theory has been used.The intensity in a lattice image can be obtained from the total wave function at the image plane is given by: where ϕg(z) is the diffracted beam amplitide given by In these equations,the z direction is perpendicular to the entrance surface, g is a reciprocal lattice vector, the Cg(i) are Fourier coefficients in the expression for a Bloch wave, b(i), X(i) is the Bloch wave excitation coefficient, ϒ(i)=k(i)-K, k(i) is a Bloch wave vector, K is the electron wave vector after correction for the mean inner potential of the crystal, T(q) and D(q) are the transfer function and damping function respectively, q is a scattering vector and the summation is over i=l,N where N is the number of beams taken into account.

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