Lecture 10 - The Mutability and Repair of DNA | Molecular Biology (DNA) by ILLL, DU - Biotechnology Engineering (BT) PDF Download

 Page 1


MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
0 
 
 
 
 
 
 
 
 
 
 
 
Molecular Biology 
 
Lesson:The Mutablility and Repair of DNA 
Lesson Developer: Dr. Aeshna Nigam 
College/Dept: Shivaji College, 
Department of Zoology 
University of Delhi 
Lesson Reviewer: Dr.Kamla Gupta 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 2


MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
0 
 
 
 
 
 
 
 
 
 
 
 
Molecular Biology 
 
Lesson:The Mutablility and Repair of DNA 
Lesson Developer: Dr. Aeshna Nigam 
College/Dept: Shivaji College, 
Department of Zoology 
University of Delhi 
Lesson Reviewer: Dr.Kamla Gupta 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
1 
 
Table of Contents 
 
 
? Introduction  
? Classification of mutations 
? Effect of Mutations 
? Mutagens 
? Physical mutagens 
? Chemical mutagens 
? Biological mutagens 
? DNA repair system 
? Direct reversal of DNA damage 
? Photoreactivation 
? Excision repair 
? Double strand break repair 
? Error in DNA repair mechanism-human diseases 
? Summary  
? Exercise/ Practice 
? Glossary 
? References/ Bibliography/ Further Reading 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 3


MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
0 
 
 
 
 
 
 
 
 
 
 
 
Molecular Biology 
 
Lesson:The Mutablility and Repair of DNA 
Lesson Developer: Dr. Aeshna Nigam 
College/Dept: Shivaji College, 
Department of Zoology 
University of Delhi 
Lesson Reviewer: Dr.Kamla Gupta 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
1 
 
Table of Contents 
 
 
? Introduction  
? Classification of mutations 
? Effect of Mutations 
? Mutagens 
? Physical mutagens 
? Chemical mutagens 
? Biological mutagens 
? DNA repair system 
? Direct reversal of DNA damage 
? Photoreactivation 
? Excision repair 
? Double strand break repair 
? Error in DNA repair mechanism-human diseases 
? Summary  
? Exercise/ Practice 
? Glossary 
? References/ Bibliography/ Further Reading 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
2 
 
Introduction 
Inheritance is the transmittance of genetic trait successfully from parents to 
offspring. This occurs through genes, which are located on chromosomes in 
higher organisms. In order to ensure that the information on these genes is 
preserved, several mechanisms have evolved to ensure that it is transmitted from 
generation to generation. Nevertheless sudden ‘changes’ or ‘variability’ do arise in 
the genetic material. These changes if inherited are termed as mutations. Thus 
mutation can be defined as, any heritable change in the DNA sequence. The 
changes in DNA may also occur in somatic cells. However these mutations are of 
importance to the organism itself as such changes are not inherited and thus 
have no evolutionary significance. Such changes are termed as somatic 
mutations. 
 
The proper functioning of the living cells requires the correct input from a number 
of genes. A high mutation rate would create havoc in working machinery of the 
genes of any organism, disrupting transmission of genetic information to the next 
generation. A common example is the cancerous cells, which undergo 
uncontrolled cell division as a result of mutation in those genes that regulate cell 
cycle. Another common example is that of sickle cell anemia. In this disease a 
point mutation results in change in structure of haemoglobin, which causes 
severe anemic condition that often results in death. 
 
But low mutation rate is always welcome as it introduces some variability in the 
genome. These genetic variability act as the raw material for evolution, from 
which mutated genes are chosen which can adapt to changing environment. This 
results in formation of new species.  Thus low mutation rate and an efficient 
repair system help to maintain diversity in nature. 
Mutations may be introduced due to error in DNA replication or chemical damage 
to the DNA sequence. The replication machinery, as studied earlier, does have an 
efficient proof reading enzyme system, which removes any of the mismatched 
nucleotides. But a few changes do evade the proof reading mechanism and thus a 
‘mismatch’ is introduced. Moreover DNA is a complex and unstable chemical 
entity, which can be assaulted by environmental changes or exposure to 
unnatural chemicals and radiations.  This causes structural changes and affects 
the base pairing ability of the altered nucleotide. These mutations affect only one 
of the parent strand of DNA, thus the mutation is introduced in only one of the 
daughter strand but carried on by two of the granddaughter molecules of the 
original parent DNA. (fig 1) 
 
Value addition: Video 
Heading text: Pure Nature Specials - Mutation - The Science 
of Survival 
Body text: watch the video in the link given below and get a glimpse of world 
of mutation from its discovery, cause how mutation works and how mutants may 
benefit future medicine. 
https://www.youtube.com/watch?v=qVmusHZtQms 
 
Page 4


MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
0 
 
 
 
 
 
 
 
 
 
 
 
Molecular Biology 
 
Lesson:The Mutablility and Repair of DNA 
Lesson Developer: Dr. Aeshna Nigam 
College/Dept: Shivaji College, 
Department of Zoology 
University of Delhi 
Lesson Reviewer: Dr.Kamla Gupta 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
1 
 
Table of Contents 
 
 
? Introduction  
? Classification of mutations 
? Effect of Mutations 
? Mutagens 
? Physical mutagens 
? Chemical mutagens 
? Biological mutagens 
? DNA repair system 
? Direct reversal of DNA damage 
? Photoreactivation 
? Excision repair 
? Double strand break repair 
? Error in DNA repair mechanism-human diseases 
? Summary  
? Exercise/ Practice 
? Glossary 
? References/ Bibliography/ Further Reading 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
2 
 
Introduction 
Inheritance is the transmittance of genetic trait successfully from parents to 
offspring. This occurs through genes, which are located on chromosomes in 
higher organisms. In order to ensure that the information on these genes is 
preserved, several mechanisms have evolved to ensure that it is transmitted from 
generation to generation. Nevertheless sudden ‘changes’ or ‘variability’ do arise in 
the genetic material. These changes if inherited are termed as mutations. Thus 
mutation can be defined as, any heritable change in the DNA sequence. The 
changes in DNA may also occur in somatic cells. However these mutations are of 
importance to the organism itself as such changes are not inherited and thus 
have no evolutionary significance. Such changes are termed as somatic 
mutations. 
 
The proper functioning of the living cells requires the correct input from a number 
of genes. A high mutation rate would create havoc in working machinery of the 
genes of any organism, disrupting transmission of genetic information to the next 
generation. A common example is the cancerous cells, which undergo 
uncontrolled cell division as a result of mutation in those genes that regulate cell 
cycle. Another common example is that of sickle cell anemia. In this disease a 
point mutation results in change in structure of haemoglobin, which causes 
severe anemic condition that often results in death. 
 
But low mutation rate is always welcome as it introduces some variability in the 
genome. These genetic variability act as the raw material for evolution, from 
which mutated genes are chosen which can adapt to changing environment. This 
results in formation of new species.  Thus low mutation rate and an efficient 
repair system help to maintain diversity in nature. 
Mutations may be introduced due to error in DNA replication or chemical damage 
to the DNA sequence. The replication machinery, as studied earlier, does have an 
efficient proof reading enzyme system, which removes any of the mismatched 
nucleotides. But a few changes do evade the proof reading mechanism and thus a 
‘mismatch’ is introduced. Moreover DNA is a complex and unstable chemical 
entity, which can be assaulted by environmental changes or exposure to 
unnatural chemicals and radiations.  This causes structural changes and affects 
the base pairing ability of the altered nucleotide. These mutations affect only one 
of the parent strand of DNA, thus the mutation is introduced in only one of the 
daughter strand but carried on by two of the granddaughter molecules of the 
original parent DNA. (fig 1) 
 
Value addition: Video 
Heading text: Pure Nature Specials - Mutation - The Science 
of Survival 
Body text: watch the video in the link given below and get a glimpse of world 
of mutation from its discovery, cause how mutation works and how mutants may 
benefit future medicine. 
https://www.youtube.com/watch?v=qVmusHZtQms 
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
3 
Source: YouTube 
 
Figure 1- Mutation alters one of the base (A->G i.e. adenine 
to guanine) that results in mutated parental DNA strand. 
First round of replication shows mutation in only one 
daughter molecule, which eventually gives rise to two 
granddaughter molecules after the second round of DNA 
replication. 
Source: Author 
 
The effects produced by mutation may have different consequences. An 
immediate consequence may be the inability of the strand to act as a template 
for transcription subsequently effecting the cell functioning. A long-term effect 
would be the permanent incorporation of this mutation in the germ line resulting 
in altered gene expression in the germ line. 
 
This chapter thus looks into the mutations and various DNA repair mechanisms to 
keep the right balance between them and wild type in nature. 
  
 
Page 5


MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
0 
 
 
 
 
 
 
 
 
 
 
 
Molecular Biology 
 
Lesson:The Mutablility and Repair of DNA 
Lesson Developer: Dr. Aeshna Nigam 
College/Dept: Shivaji College, 
Department of Zoology 
University of Delhi 
Lesson Reviewer: Dr.Kamla Gupta 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
1 
 
Table of Contents 
 
 
? Introduction  
? Classification of mutations 
? Effect of Mutations 
? Mutagens 
? Physical mutagens 
? Chemical mutagens 
? Biological mutagens 
? DNA repair system 
? Direct reversal of DNA damage 
? Photoreactivation 
? Excision repair 
? Double strand break repair 
? Error in DNA repair mechanism-human diseases 
? Summary  
? Exercise/ Practice 
? Glossary 
? References/ Bibliography/ Further Reading 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
2 
 
Introduction 
Inheritance is the transmittance of genetic trait successfully from parents to 
offspring. This occurs through genes, which are located on chromosomes in 
higher organisms. In order to ensure that the information on these genes is 
preserved, several mechanisms have evolved to ensure that it is transmitted from 
generation to generation. Nevertheless sudden ‘changes’ or ‘variability’ do arise in 
the genetic material. These changes if inherited are termed as mutations. Thus 
mutation can be defined as, any heritable change in the DNA sequence. The 
changes in DNA may also occur in somatic cells. However these mutations are of 
importance to the organism itself as such changes are not inherited and thus 
have no evolutionary significance. Such changes are termed as somatic 
mutations. 
 
The proper functioning of the living cells requires the correct input from a number 
of genes. A high mutation rate would create havoc in working machinery of the 
genes of any organism, disrupting transmission of genetic information to the next 
generation. A common example is the cancerous cells, which undergo 
uncontrolled cell division as a result of mutation in those genes that regulate cell 
cycle. Another common example is that of sickle cell anemia. In this disease a 
point mutation results in change in structure of haemoglobin, which causes 
severe anemic condition that often results in death. 
 
But low mutation rate is always welcome as it introduces some variability in the 
genome. These genetic variability act as the raw material for evolution, from 
which mutated genes are chosen which can adapt to changing environment. This 
results in formation of new species.  Thus low mutation rate and an efficient 
repair system help to maintain diversity in nature. 
Mutations may be introduced due to error in DNA replication or chemical damage 
to the DNA sequence. The replication machinery, as studied earlier, does have an 
efficient proof reading enzyme system, which removes any of the mismatched 
nucleotides. But a few changes do evade the proof reading mechanism and thus a 
‘mismatch’ is introduced. Moreover DNA is a complex and unstable chemical 
entity, which can be assaulted by environmental changes or exposure to 
unnatural chemicals and radiations.  This causes structural changes and affects 
the base pairing ability of the altered nucleotide. These mutations affect only one 
of the parent strand of DNA, thus the mutation is introduced in only one of the 
daughter strand but carried on by two of the granddaughter molecules of the 
original parent DNA. (fig 1) 
 
Value addition: Video 
Heading text: Pure Nature Specials - Mutation - The Science 
of Survival 
Body text: watch the video in the link given below and get a glimpse of world 
of mutation from its discovery, cause how mutation works and how mutants may 
benefit future medicine. 
https://www.youtube.com/watch?v=qVmusHZtQms 
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
3 
Source: YouTube 
 
Figure 1- Mutation alters one of the base (A->G i.e. adenine 
to guanine) that results in mutated parental DNA strand. 
First round of replication shows mutation in only one 
daughter molecule, which eventually gives rise to two 
granddaughter molecules after the second round of DNA 
replication. 
Source: Author 
 
The effects produced by mutation may have different consequences. An 
immediate consequence may be the inability of the strand to act as a template 
for transcription subsequently effecting the cell functioning. A long-term effect 
would be the permanent incorporation of this mutation in the germ line resulting 
in altered gene expression in the germ line. 
 
This chapter thus looks into the mutations and various DNA repair mechanisms to 
keep the right balance between them and wild type in nature. 
  
 
MUTABILITILY AND REPAIR OF DNA 
Institute of Lifelong Learning, University of Delhi 
4 
 
 
Classification of mutations 
Mutation is alteration in DNA sequence. The extent to which a mutation changes 
the characteristics of an organism depends upon where the mutation has 
occurred and the degree to which it has altered the gene. Mutation can be 
classified in various ways: 
A. Location of gene where mutation occurred 
i. Autosomal mutation: occur within genes of autosomes. 
ii. X-linked mutation: occur within gene of X-chromosome. 
B. Location of cell 
i. Somatic mutation: occur in any body cell other than gametes 
ii. Germline mutation: occur in gametes. 
C. Factor based 
i. Spontaneous mutation: that happens naturally like random changes in 
nucleotide sequence. 
ii. Induced mutation: that happens due to external factors like physical/ 
chemical/ biological agents. 
D. Location of mutation 
i. Gene: mutation occurs in gene. Gene mutation can further be subdivided into: 
a. Point mutation or base pair substitution 
b. Frameshift mutation