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3.3 DNA replication

a rate that would result in each cell accumulating many mutations per day if there were not constant repair. Some types of damage occur spontaneously, while other types are caused or accelerated by external factors, such as chemicals and radiation, or internal fac tors, such as reactive oxygen species (also called free radicals) gen erated during cellular respiration. Some examples of DNA damage are illustrated in Figure 3.25. Such damage can interfere with transcription (copying the DNA sequence to RNA for protein synthesis) and with DNA replication.

organism ages. This means that telomeres shorten gradually dur ing successive cell divisions, but important sequences at the ends of chromosomes are protected. It is suggested that shortening of our telomeres may be connected to the ageing process. DNA suffers frequent damage, but can be repaired The mechanisms described above ensure that DNA is replicated accurately. However, chemical changes that damage DNA occur at

CH 3

(a)

O

O

N

P

P

N

NH

N

G

CH 2

CH 2

N

N

O

O

NH 2

NH 2

N

Alkylation

N

NH 2

P

P

N

N

A

CH 2

CH 2

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OH

O

O

N

Depurination

O

NH 2

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P

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NH

U

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CH O 2

CH O 2

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N

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Deamination

P

P

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Thymine

H

P

P

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H

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O

O

N

C

N

C

C O

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N

C O

C

C

UV radiation

C

C

CH 3

H

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H

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P

H

CH

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3

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O

O

N

C

N

C O

C O

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C

C

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H

CH

CH 3

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H

Thymine dimer

DNA strand

Thymine

DNA strand

Figure 3.25 Examples of DNA damage. (a) A sequence of undamaged DNA is shown on the left. On the right, each base has undergone a different form of damage. In reality, adjacent bases are unlikely to undergo different types of damage at the same time: this is shown for illustration. Alkylation is the addition of a methyl or ethyl group to the base by a chemical agent. Here, guanine (G) is methylated (yellow highlight). The resulting O6-methylguanine mispairs with thymine during DNA replication, causing a mutation. Depurination , through cleavage of the glycosidic bond that links adenine or guanine to the deoxyribose sugar, and deamination of cytosine, adenine, or guanine are common types of spontaneous DNA damage. Deamination of cytosine creates uracil (U), as shown. (b) Exposure to ultraviolet (UV) light can cause fused structures of adjacent pyrimidine bases such as the thymine dimer shown. Source : (a) Adapted from Cooper G. M. (2000) The Cell: A Molecular Approach , 2nd edn. Sinauer Associates, Sunderland (MA); and Essential Cell Biology , 4th edn. (b) Alberts et al. Essential Cell Biology , 5th edn. W.W. Norton and company, 2019.

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