DNA Replication Steps: 5 Important Concepts


Contents

What is the first step in DNA replication?

The process of DNA replication is usually completed into three steps, namely: Initiation, Elongation, and Termination. 

The Initiation is the first among the DNA replication steps. The associated proteins, enzymes, and the remaining factors recognize some specific sites in the DNA, known as the origin of replication, and trigger the replication process.

The Initiation step of DNA replication takes place in the following sequel:

  • Starts at specific points inside the DNA strand called” origins of replication,” (recognized by specific nucleotide sequences or codes).
  • Origin of replication) are recognized by initiator proteins
  • Initiator proteins call more proteins that support the replication process, framing a replication complex around the replication origin in the DNA. 
  • There are generally multiple sites for the origin of replication, and these localized sites are known as replication forks (Y shaped structure). 
  • Each origin of replication has a twin replication fork, moving away from that equivalent point of origin of replication to either end of the DNA double helix.
  • DNA Helicase, which loosens up the DNA double helix and segregates the two strands to be utilized as a template strand for the synthesis of a new DNA strand (replica).
  • Unwinding of DNA occurs by hydrolyzing the ATP.
  • Single-strand binding proteins (SSB) work with helicase to keep the parental DNA double helix in the unwounded state.
  • DNA Primase incorporates a small-length RNA primer, which goes about as an ‘initiator’ for DNA Polymerase.
  • This DNA Polymerase extend the new strands of DNA by recognizing RNA primers.
  • DNA polymerase, performs the synthesis in the order of 5′ to 3′.
  • One adds nucleotides individually toward the replication fork, and the other is ready to add just in fragments.
  • The strand in which nucleotides are added constantly is known as the leading strand, while the other strand, synthesized in the form of fragments, is known as the lagging strand.

Which steps in replication of DNA involves ATP?

There are several occasions in the DNA replication process where the consumption, transaction, or involvement of ATP is observed. 

There are specific enzymes like helicases involved in the replication process that utilize ATP to perform their function of unwinding DNA double helix. ATP is also used in phosphorylating DNA replication enzymes when a new nucleotide attaches to the growing DNA strand.

Following are the ATP utilizing steps of the replication process:

  • DNA helicases are basically ATP utilizing enzymes that unwind and separate the two parental strands and eventually give rise to the replication forks, which dynamically move away from the origin site. The DNA helicase hydrolyzes ATP while binding to single strands of DNA. 
  • Another place, During the DNA polymerization, DNA polymerase promotes the synthesis of phosphodiester bond hydrolyzed by 2 Phosphate molecules gave by (beta and gamma) Phosphate straightforwardly got from dNTPs most usually ATP.

What is DNA replication in biology?

DNA replication is an essential process for the living organisms to sustain as it is a prerequisite for cell division

DNA replication is the interaction by which two-fold DNA is duplicated to create two DNA strands identical in nature. Replication is a fundamental DNA process because the two newly formed cells should contain similar DNA as the parent cell at whatever point of cell division. 

Following is the brief description about the process of replication:

  • DNA replication starts at an exact point, called the origin of replication, where the unwinding of DNA twofold helix starts.
  • A short section of RNA, known as primer, is then formed and goes about as a beginning stage for the synthesis of DNA.
  • A protein called DNA polymerase next starts replicating the DNA by coordinating with bases to the first strand.
  • When replication is finished, the RNA primer is supplanted with DNA, and any gap between recently formed DNA strand are fixed along with enzymes.
  • DNA replication is a critical process; in this manner, the cell edits the recently incorporated DNA to guarantee that errors, or mutations, are not presented.
  • When the DNA in a cell is reproduced, the cell can separate into two compartments, each with an indistinguishable (identical) copy of the first DNA.

How is the DNA replication process responsible for the preservation of heredity?

The process of DNA replication preserves the genome integrity as well as the heredity. The secret is present in the pattern of DNA replication.

DNA replication is when the cell duplicates its DNA, and the DNA is subsequently split between two newly formed cells. When the DNA duplicates, it occurs during the S period of the cell cycle (S denotes Synthesis). These means have a place both in Mitosis and Meiosis I. 

The process of DNA replication preserves heredity (genetic integrity) in the following ways:

  • The two replicas are made from the newly synthesized DNA and the old-DNA strand utilized as a template for the daughter DNA strand. In this manner, the two daughter cells will have the “ same DNA “ ( I mean a similar sequence ) as the parent cells. 
  • Many editing components exist during the DNA replication, which implies measures that can recognize a mistake during the replication and ultimately rectify it. This ensures that similar genetic information conveyed by the parent cell is sent to its daughter cells mistake-free. 
  • The DNA polymerase itself has an editing/proof-reading feature. If a mistake happens, it goes back and erases (like the erase key on your PC ) some unacceptable base just added. 
  • Be that as it may, in some cases, mistakes are not recognized, and when not eradicated, some unacceptable base added can bring about a mutation and saying the mutation will be “fixed.”

What is a primer in DNA replication?

Primer is required to start the replication process as the DNA polymerase requires an RNA primer to initiate the DNA synthesis.

A primer is a short sequence of ribonucleic acid (RNA) that begins DNA replication. In living life forms, primers are short fragments of RNA. The primer should be formed with the help of an enzyme known as primase. It is a kind of RNA polymerase before DNA replication can happen. 

Forming a primer is essential because the enzymes that replicate DNA, called DNA polymerases, can join new DNA nucleotides to a current strand of nucleotides. The primer hence serves to prime and establish a foundation for DNA replication.

The primer is taken out before DNA replication is finished, and the gaps in the DNA strand are filled with the help of DNA polymerases. The primers can also be designed and optimized with exact nucleotide sequences complementary to the template DNA strand. In the process of Polymerase chain reaction, DNA primers are utilized.

Figure: DNA polymerase requires RNA primers to start the replication process. Image Credit: Wikimedia

What are some inhibitors of DNA replication?

DNA replication inhibitors are regularly utilized in anticancer and antiviral formulations. Inhibitors hinder DNA replication in two interrelated ways: 

•        Directly interacting with prerequisites needed for DNA polymerization and replication origin

•        Interfering in the checkpoints. The immediate destination for “pharmacological targets” includes cyclin-dependent kinases, DNA templates, DNA polymerases, Chain Elongation, Nucleotide precursor pools. 

Following are some reasons why checkpoints are important during cell division and DNA replication process:

  • The checkpoint (“Intra S-stage”) response was first recognized for its inadequacy in quite a while from patients with Ataxia Telangiectasia (AT).
  • These checkpoints permit the maintenance of the inhibitor-initiated DNA damage.
  • These checkpoints can likewise trigger Apoptosis (Programmed cell death).
  • Practically, checkpoint response can be distinguished from direct replication block when replication hindrance can be eased by designated checkpoint inhibitors, for example, Chk1 or Chk2, ATM/ATR  inhibitors.
Figure: Possible approaches to inhibit the DNA replication process. Image Credit: Wikimedia

Dr. Abdullah Arsalan

I am Abdullah Arsalan , Completed my PhD in Biotechnology. I have 7 years of research experience. I have published 6 papers so far in the journals of international repute with an average impact factor of 4.5 and few more are in consideration. I have presented research papers in various national and international conferences. My subject area of interest is biotechnology and biochemistry with special emphasis on Protein chemistry, enzymology, immunology, biophysical techniques and molecular biology. Let's connect through LinkedIn(https://www.linkedin.com/in/abdullah-arsalan-a97a0a88/) or Google scholar(https://scholar.google.co.in/citations?user=AeZVWO4AAAAJ&hl=en).

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