DNA polymerase is fast and accurate, but it makes mistakes.

For example, it might read A and place a C across from it where it should have placed a T.

If nothing were done to correct such errors, each generation of cells could have thousands of faulty proteins, coded for by DNA that had been miscopied.

To prevent such catastrophic damage to the cell, there are multiple modes of correcting replication errors, collectively called the DNA damage response (DDR).

DNA polymerase itself double-checks the new base pair and tends to replace incorrect, biochemically unstable pairs with more stable, correct pairs-for example, removing C and replacing it with T.

As a result, only one mistake remains for every billion base pairs replicated-a very high degree of replication accuracy, if not completely flawless.

Changes in DNA structure, called mutations, can result from replication errors or from environmental factors such as radiation, chemicals, and viruses.

Uncorrected mutations can be passed on to the descendants of that cell, but many of them have no adverse effect.

One reason is that a new base sequence sometimes codes for the same thing as the old one. For example, TGG and TGC both code for threonine (see table 4.2), so a mutation from G to C in the third place wouldn't necessarily change protein structure.

Another reason is that a change in protein structure isn't always critical to its function.

the beta chain of hemoglobin is 146 amino acids long in both humans and horses,

25 of these amino acids differ between the 1 species. Nevertheless, the hemoglobin is funcrional in both species

Furthermore, since 98% of the DNA doesn't code for any proteins, the great majority of mutations don't affect protein structure at all.

Other mutations, however, may kill a cell, turn it cancerous, or cause genetic defects in future generations.

When a mutation changes the sixth amino acid of ẞ-hemoglobin from glutamic acid to valine, for example, the result is a crippling disorder called sickle-cell disease. Clearly some amino acid substitutions

are more critical than others, and this affects the severity of a mutation. More than 30 diseases are known to result from defects in the DNA damage response, including some forms of anemia, cancer, immune deficiency, and brain defects.

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Question	Answer
DNA polymerase is fast and accurate, but it makes mistakes.	For example, it might read A and place a C across from it where it should have placed a T.
If nothing were done to correct such errors, each generation of cells could have thousands of faulty proteins, coded for by DNA that had been miscopied.	To prevent such catastrophic damage to the cell, there are multiple modes of correcting replication errors, collectively called the DNA damage response (DDR).
DNA polymerase itself double-checks the new base pair and tends to replace incorrect, biochemically unstable pairs with more stable, correct pairs-for example, removing C and replacing it with T.	As a result, only one mistake remains for every billion base pairs replicated-a very high degree of replication accuracy, if not completely flawless.
Changes in DNA structure, called mutations, can result from replication errors or from environmental factors such as radiation, chemicals, and viruses.	Uncorrected mutations can be passed on to the descendants of that cell, but many of them have no adverse effect.
One reason is that a new base sequence sometimes codes for the same thing as the old one. For example, TGG and TGC both code for threonine (see table 4.2), so a mutation from G to C in the third place wouldn't necessarily change protein structure.	Another reason is that a change in protein structure isn't always critical to its function.
the beta chain of hemoglobin is 146 amino acids long in both humans and horses,	25 of these amino acids differ between the 1 species. Nevertheless, the hemoglobin is funcrional in both species
Furthermore, since 98% of the DNA doesn't code for any proteins, the great majority of mutations don't affect protein structure at all.	Other mutations, however, may kill a cell, turn it cancerous, or cause genetic defects in future generations.
When a mutation changes the sixth amino acid of ẞ-hemoglobin from glutamic acid to valine, for example, the result is a crippling disorder called sickle-cell disease. Clearly some amino acid substitutions	are more critical than others, and this affects the severity of a mutation. More than 30 diseases are known to result from defects in the DNA damage response, including some forms of anemia, cancer, immune deficiency, and brain defects.

Created by: Russells3709

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