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Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Overview of DNA Repair02:25

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In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
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Base Excision Repair01:54

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One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
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Negative Regulator Molecules01:23

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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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Transcription01:10

Transcription

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Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
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Single Cell Analysis Of Transcriptionally Active Alleles By Single Molecule FISH
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Transcription-Coupled Repair: From Cells to Single Molecules and Back Again.

T R Strick1, J R Portman2

  • 1Institut Jacques Monod, CNRS and Université Paris 7, Paris Université, Paris, France; Institut de Biologie de l'Ecole normale supérieure, PSL Université, INSERM, CNRS, Paris, France; Equipe Labellisée de la Ligue Nationale Contre le Cancer, Paris, France; Horizons 2020 Innovative Training Network, DNAREPAIRMAN, Paris, France.

Journal of Molecular Biology
|June 9, 2019
PubMed
Summary

The Mfd protein is crucial for transcription-coupled repair (TCR), a process that preferentially repairs DNA damage on transcribed gene strands. This review details Mfd

Keywords:
R-loopsevolutionmutagenesissingle-moleculestranscription-coupled repair

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Area of Science:

  • Molecular Biology
  • DNA Repair Mechanisms
  • Genetics

Background:

  • Transcription-coupled repair (TCR) preferentially repairs DNA lesions in the transcribed strand of active genes.
  • Global genome repair (GGR) is a distinct, strand-aspecific DNA repair pathway.
  • The Mfd protein is central to mediating TCR.

Purpose of the Study:

  • To review the genetic discovery of the Mfd gene.
  • To summarize biochemical, structural, and single-molecule studies of the Mfd protein.
  • To explore Mfd's role in mutagenesis.

Main Methods:

  • Genetic analysis leading to Mfd gene identification.
  • Biochemical assays to characterize Mfd protein function.
  • Structural biology and single-molecule techniques for Mfd interrogation.
  • Mutagenesis studies to investigate Mfd's role in DNA damage response.

Main Results:

  • Mfd protein binds stalled RNA polymerase at DNA lesions, displacing it and recruiting repair factors (UvrA, UvrB).
  • The TCR pathway involves UvrC (excision), UvrD (oligonucleotide removal), DNA polymerase (filling), and DNA ligase (sealing).
  • Mfd was initially identified through the 'mutation frequency decline' phenotype, linked to enhanced TCR of UV lesions in tRNA genes.

Conclusions:

  • The Mfd protein is essential for the transcription-coupled DNA repair pathway.
  • Understanding Mfd's mechanism provides insights into maintaining genome integrity during transcription.
  • Recent findings highlight Mfd's involvement in cellular mutagenesis processes.