DNA replication

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DNA replication

Michael Kallsen

Michael Kallsen

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Flashcards

DNA replication

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Questions

USMLE® Step 1 style questions USMLE

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DNA replication is a highly complex process where replication occurs on both strands of DNA. On the leading strand of DNA, replication occurs uninterrupted, but on the lagging strand, replication is interrupted and results in the synthesis of Okazaki fragments that need to be joined. Which of the following enzymes is involved in the penultimate step before ligation of Okazaki fragments?  

Transcript

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At a quick glance, the life of a cell - it’s cell cycle - is pretty routine.

It’s either actively dividing, or preparing to divide into two daughter cells.

The cell cycle itself has an interphase, made up of subphases G1, S and G2, during which the cell is preparing for division, and mitosis, during which the cell actively divides.

During the S phase, the cell performs DNA replication - which is when its 46 chromosomes are duplicated so that each daughter cell can get its own copy of the genetic material.

A single chromosome is made up a single DNA molecule that has two strands, which wrap one around one another to form a double helix.

Each single strand of DNA is composed of a sequence of four types of nucleotides - which are the individual letters or building blocks of DNA.

Nucleotides of DNA are made up of a sugar - deoxyribose, a phosphate, and one of the four nucleobases - adenine, cytosine, guanine, and thymine - or, commonly, A, C, G, T for short.

The nucleotides on one strand form hydrogen bonds to complementary nucleotides on the other strand; specifically, A bonds with T via two hydrogen bonds, and C bonds with G, via three hydrogen bonds.

Additionally, the two DNA strands also have a “direction” - meaning, one of them runs from the 3’ end to the 5’ end, while the other one runs from the 5’ end to the 3’ end.

Kinda like two snakes coiled up together, but facing in different directions.

DNA replication can be described as semiconservative.

That means that each strand of the double helix acts as a “template”, based on which a new, complementary strand will form.

Eventually the original chromosome will split into two exact copies, each made of one of original strands, and one of the newly made ones.

Overall, DNA replication has 3 steps: initiation, elongation, and termination.

Initiation kicks off when a group of proteins get together to form the pre-replication complex.

This pre-replication complex looks for specific nucleotide sequences along the DNA strand - called origins of replication.

And yes, we’re talking plural! That’s because our DNA strand is so long that DNA replication actually starts in several origins along the chromosomes simultaneously.

These special nucleotide sequences have a ton of A and T bases.

Because A and T are joined by only two hydrogen bonds, the enzyme DNA helicase has a relatively easy time separating the two strands.

This creates a replication fork, with the two prongs of the fork being the two strands that are separate from one another.

Single strands of DNA can get a bit unstable, so to help keep them from getting back together again, helper molecules called single stranded DNA binding proteins come in and bind to each of the lonely strands.

Also, as DNA helicase breaks down bonds, the segments of DNA ahead of it start to overwind - meaning, the double helix becomes more tightly wound.

You can try this with a close friend who has braided hair - if you pull the braid apart in the middle then the ends get tighter.

Again - make sure it’s a friend and not a stranger.

Overwinding of the DNA can slow down replication, so the enzyme DNA topoisomerase works ahead of DNA helicase to loosen up the tight DNA coils.

It achieves this by gently snapping one strand, loosening the overwinding tension, and then patching it back up, tension free.

The second step is elongation, and for that we need a new enzyme - RNA primase. Yes, you heard that correct, RNA this time.

It’s kinda like DNA, it uses ribose instead of deoxyribose in its nucleotides, and instead of thymine, it uses uracil.

Key Takeaways

DNA replication is the process by which a DNA molecule is copied into two identical DNA molecules. This process is essential to ensure the accurate transmission of genetic information from one generation to the next.

DNA replication occurs in three main steps: initiation, elongation, and termination. Initiation involves the unwinding of the DNA molecule, and it happens thanks to DNA helicase and topoisomerase enzymes. Next, elongation consists of making RNA primers by RNA primase and synthesizing the DNA leading strand by DNA polymerase. In termination, converging replication forks meet, and the whole process is complete.