When Nucleotide Excision Repair Occurs, In Which Order Do Enzymes Function?

Deoxyribonucleic acid replication and repair

Final updated

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January 31, 2022

Summary

Cell division involves the duplication of a cell's entire Dna so that two genetically identical daughter cells arise from a single prison cell. Dna is spring to proteins in the nucleus and is tightly packed. Therefore, DNA replication requires that the DNA is loosened and the double helix is unwound. Specific proteins, including DNA polymerase, then synthesize a complementary daughter strand of double-stranded Deoxyribonucleic acid (dsDNA) from each unmarried strand template. This leads to the germination of ii dsDNA molecules, each composed of 1 new and i original strand. The process of DNA replication includes control mechanisms to continue the genetic information as stable every bit possible, but errors (e.g., the incorporation of a wrong base) however occur. External factors as well as internal cellular processes lead to alterations in the chemical structure of Dna. Unrepaired Dna errors can cause mutations and/or prison cell devastation. Deoxyribonucleic acid repair mechanisms are, therefore, important to ensure genomic stability.

DNA replication

H elicase divides DNA into ii H alves. Liga se Liga tes the Okazaki fragments!

Initiation

1. Origin of replication (ori): a specific Deoxyribonucleic acid sequence in the genome where DNA replication starts
   • Specific proteins (comprising a prepriming complex) recognize and demark to the origin of replication.
   • The origin of replication contains AT-rich sequences (e.k., TATA box regions), similar to those institute in promoters
   • Prokaryotes with round genomes have a single origin.
   • Eukaryotes take numerous oris (e.grand., 30,000–50,000 in humans) at which DNA replication begins simultaneously.
2. Replication fork : Y-shaped region in the chromosome where both leading and lagging strands are replicated from the DNA template
   • Helicase separates and begins unwinding dsDNA into single strands at the ori , forming ii replication forks .
   • Replication occurs on both strands simultaneously (bidirectionally), merely always in a 5′ → iii′ directiodue north.
3. Prevention of reannealing: SSBs prevent the single strands from reannealing and protect ssDNA from cleavage.
4. Supercoil relaxation : : DNA topoisomerases salve overwinding (positive supercoils ) or underwinding (negative supercoils ) that develop during Deoxyribonucleic acid separation and elongation.

Elongation

1. Primer synthesis
   • RNA primers : a 10–12 nucleotides long RNA sequence that is complementary to the template strand
     • Synthesized by RNA primase
     • Provide a 3′-OH group to which Deoxyribonucleic acid polymerases tin adhere a Dna nucleotide.
   • The RNA primer is removed at a later phase.
2. Deoxyribonucleic acid synthesis : For simultaneous replication of both parent strands, DNA replication occurs continuously on the leading strand and discontinuously on the lagging strand in a 5′→3′ direction . At the aforementioned fourth dimension, complementary deoxynucleotides are added to the free 3′-OH group of the girl strand.
   • Reaction catalyzed by DNA polymerase ( polymerase δ in eukaryotes , Deoxyribonucleic acid polymerase Iii in prokaryotes )
     • 5′→3′ Deoxyribonucleic acid polymerase activity catalyzes the nucleophilic attack of the iii′-OH group on the α-phosphate of the incoming deoxynucleotide triphosphate, forming an ester bail.
     • DNA strands are elongated by i nucleotide at a time.
     • Pyrophosphate (PP_i) is released.
     • Pyrophosphate is broken into ii phosphates by pyrophosphatase.
   • Leading strand : a complementary daughter strand of Dna whose replication is continuous due to its free iii′-OH end
     • The free 3′-OH end is initially on the primer.
     • Only one primer is required.
   • Lagging strand : a complementary daughter strand of DNA whose replication is discontinuous because new RNA primers are constantly existence synthesized at the moving replication fork to ensure a free 3′-OH finish for elongation
     • Okazaki fragments ; : discontinuous segments of 1,000–2,000 nucleotides that ascend during lagging strand creation
3. Proofreading : Some polymerases (east.k., DNA polymerase I and 3) take ; 3′→five′ exonuclease activity to proofread recently synthesized Dna and to remove incorrectly paired nucleotides .
4. Primer removal :
   • Deoxyribonucleic acid polymerase I and δ have v'→3' exonuclease activeness that enables the enzymes to remove the RNA primer.
   • In prokaryotes ; , by RNase H and 5′→3′ exonuclease activity of DNA polymerase I . In eukaryotes, the RNA primer is displaced by Dna polymerase δ and excised by the enzyme FEN-1 ( flap endonuclease-1 )
5. Filling the gaps : During primer removal, Deoxyribonucleic acid polymerase fills the gaps with deoxynucleotides complementary to the parent strand until the gratuitous ends meet.
   • In prokaryotes, Deoxyribonucleic acid polymerase I replaces the RNA primer by adding deoxynucleotides ane at a time and proofreads equally it does so.
   • In eukaryotes, polymerase δ replaces the RNA primer.
     • DNA ligase joins (ligates) the free ends of Okazaki fragments , resulting in a continuous strand of Deoxyribonucleic acid.
     • Ligase reaction
       • Dna ligase transfers an AMP residue to the 5′ phosphate end of 1 of the Dna fragments to be bound.
       • AMP is cleaved and the 5′ phosphate end is leap to the 3′-OH stop of the other fragment.

Termination

Dna replication inhibitors have a modified 3′-OH end that prevents the elongation of the existing nucleotide chain, a phenomenon besides known every bit "chain termination."

Telomeres

To remember the TTAGGG sequence added by the tel omerase: Tel l T hem A ll: K enes G otta Thousand o!

Mechanisms of Dna damage

DNA repair mechanisms

References

1. Bregje van Oorschot, Giovanna Granata, Simone Di Franco, Rosemarie X Cate, Hans M Rodermond, Matilde Todaro, Jan Paul Medema, Nicolaas A P Franken. Targeting Deoxyribonucleic acid double strand break repair with hyperthermia and Dna-PKcs inhibition to enhance the effect of radiation treatment. Oncotarget. 2016 .
2. Susan S. Wallace, Ph.D, Drew 50. Tater, Ph.D., and Joann B. Sweasy, Ph.D.. Base Excision Repair and Cancer. Cancer Messages. 2012 .

Source: https://www.amboss.com/us/knowledge/DNA_replication_and_repair

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