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Mechanical Protein Functions01:58

Mechanical Protein Functions

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Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force. 
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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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Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
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DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
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DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied.  After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
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Determining Membrane Protein Topology Using Fluorescence Protease Protection FPP
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DNA Mechanics and Topology.

Sumitabha Brahmachari1, John F Marko2

  • 1Northwestern University, Evanston, IL, USA.

Advances in Experimental Medicine and Biology
|October 29, 2018
PubMed
Summary

This review explores DNA mechanics, from base pairs to chromosomes, detailing how polymer physics, protein interactions, and topological constraints influence DNA behavior and its relevance to oncology.

Keywords:
BraidDNA mechanicsDNA topologyDNA–protein interactionsLengthwise compaction.Linking numberPlectonemeSupercoilingWorm-like chain

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Polymer Physics

Background:

  • Understanding the physical properties of DNA and its interactions with proteins is crucial for comprehending cellular processes.
  • DNA's mechanical behavior is influenced by its structure, topology, and associated proteins, impacting its function in vivo.

Purpose of the Study:

  • To provide a comprehensive review of the mechanics of DNA and DNA-protein complexes across various scales.
  • To highlight the role of polymer statistical mechanics and topological constraints (entanglement, supercoiling) in DNA behavior.
  • To discuss the implications of DNA physical properties and chromatin organization in the context of oncology.

Main Methods:

  • Review of single-molecule experiments elucidating DNA double helix mechanics.
  • Discussion of theoretical models for protein-DNA interactions and their effects on DNA polymer properties.
  • Analysis of mechanisms controlling DNA topology, including compaction machinery and topoisomerases.

Main Results:

  • Detailed description of DNA double helix mechanics informed by polymer statistical mechanics.
  • Explanation of how topological constraints like entanglement and supercoiling affect DNA's physical and mechanical responses.
  • Models illustrating DNA-bending protein interactions and their impact on DNA-protein complex behavior in vivo.

Conclusions:

  • The physical properties of DNA and chromatin are intrinsically linked to their biological functions.
  • Understanding DNA mechanics provides insights into cellular processes and disease mechanisms, particularly in oncology.
  • Topological regulation and protein interactions are key determinants of DNA behavior within the cell.