BASE ANALOGUE

MUTAGENS
PRESENTD BY SAWERA SHAFIQ

Session 2020-24 BS Zoology 8th Semester

TABLE OF
CONTENT
Here the table of contents shows:

01 Introduction 04 General Effects

02 Examples 05 Biological Implications

03 Mechanism of Action 06 Safety and Handling

BASE ANALOGUE MUAGENS
INTRODUCTION

Base analogue mutagens are chemical

compounds that are structurally similar to the
normal bases found in DNA. These analogues
can be incorporated into DNA during
replication, where they may cause mutations
due to their ability to pair incorrectly with the
natural bases. These mutagens are chemicals
that mimic the structure of natural DNA bases
but have subtle differences that lead to
increased mutagenesis.
 EXAMPLES
Here are some examples along with their effects:
1. 5-Bromouracil (5-BU)
Structure and Mechanism:
• 5-Bromouracilis an analogue of thymine (T). It can pair with
adenine (A) like thymine does, but it can also pair with
guanine (G) due to its keto-enol tautomerism.
• In its keto form, 5-BU pairs with adenine. When it shifts to
its enol form, it can pair with guanine.
Mutagenic Effect:
• During DNA replication, if 5-BU is incorporated instead of
thymine, it pairs with adenine. However, if it shifts to its
enol form in a subsequent round of replication, it can pair
with guanine.
• This can result in an AT to GC transition mutation over
successive generations of DNA replication.
 2. 2-Aminopurine (2-AP)
Structure and Mechanism:
• 2-Aminopurine is an analogue of adenine. It can pair
with thymine (T) or cytosine (C).
• The ambiguity in pairing arises because 2-AP can
form hydrogen bonds with either T or C, depending
on its protonation state.

Mutagenic Effect:
• When 2-AP is incorporated into DNA, it may pair with
thymine. However, during the next round of replication,
if it shifts to pair with cytosine, this leads to an AT to GC
transition mutation.
• Alternatively, if it originally pairs with cytosine and later
shifts to pair with thymine, it results in a GC to AT
transition mutation.
CONTINUE..
3. 5-Fluorouracil (5-FU)
Structure and Mechanism:
• 5-Fluorouracil is another analogue of
thymine. It is often used in chemotherapy
for its ability to inhibit thymidylate synthase,
which is crucial for DNA synthesis.
• However, when incorporated into DNA, it
behaves similarly to 5-BU, potentially
pairing with both adenine and guanine.

Mutagenic Effect:
• Like 5-BU, 5-FU can induce AT to GC
transition mutations due to its ability to
pair ambiguously with adenine and
guanine.
CONTINUE..
4. 5-Iodouracil (5-IU)
Structure and Mechanism:
• 5-Iodouracilis similar to 5-BU and is an
analogue of thymine. It can also undergo
tautomeric shifts, allowing it to pair with
adenine or guanine.
Mutagenic Effect:
• Incorporation of 5-IU into DNA can cause
AT to GC transition mutations as it
alternates between pairing with adenine
and guanine.
MECHANISM OF 01 1. Structural Mimicry and Incorporation:

ACTION Base analogue mutagens resemble natural

nucleobases (adenine, thymine, cytosine, or
guanine) closely enough to be incorporated into
DNA during replication. DNA polymerases cannot
easily distinguish these analogues from the normal
bases, leading to their incorporation into the
growing DNA strand
02 2. Tautomeric Shifts:

Many base analogues can exist in multiple

tautomeric forms. Tautomers are isomers of a
compound that differ only in the position of
protons and electrons. For example, keto and enol
tautomers differ in the placement of a hydrogen
atom and a double bond.
MECHANISM OF The tautomeric form that predominates can affect
base-pairing properties. A tautomeric shift can
ACTION occur between the time of incorporation and
subsequent rounds of replication, leading to
mispairing and mutations.

03 Mispairing
When a base analogue is incorporated into DNA, it
may form base pairs with the correct
complementary base during the initial replication.
However, due to tautomeric shifts or intrinsic
properties, it may form base pairs with incorrect
bases in subsequent replications.
This mispairing leads to point mutations, specifically
transition mutations, where one purine (A or G) is
substituted for another purine, or one pyrimidine (T
or C) is substituted for another pyrimidine.
GENERAL EFFECTS

Transition Mutations Replication Errors Mutagenesis

Most base analogue mutagens They increase the likelihood of These agents can be potent
cause transition mutations replication errors because mutagens, leading to changes in
(purine to purine or they can pair with multiple the genetic code that may result
pyrimidine to pyrimidine bases. in altered protein function, loss of
substitutions), as seen with 5- gene function, or sometimes
BU and 2-AP. beneficial mutations.
 CONTINUE..

Chemotherapy Applications

• Some base analogues, like 5-FU, are used in

chemotherapy due to their ability to disrupt
DNA synthesis in rapidly dividing cancer
cells.
• Overall, base analogue mutagens are
crucial tools in molecular biology and
genetics, providing insight into the
mechanisms of DNA replication and
mutation. Their study has also contributed
to the development of therapeutic agents
for cancer treatment.
 2. Cancer:
BIOLOGICAL
IMLICATIONS : In multicellular organisms, base analogue-
induced mutations can lead to cancer if they
occur in genes that regulate cell growth and
Here are given important biological imlications division (oncogenes and tumor suppressor
of Base Analogue Mutagens.. genes).

1. Mutagenesis: 3. Research Tools:

Base analogues can induce mutations in various

Despite their mutagenic potential, base
organisms, including bacteria, yeast, and higher
analogues are also valuable tools in molecular
eukaryotes. These mutations can be beneficial,
biology and genetics research for studying
neutral, or deleterious depending on the context
mutation processes and DNA repair
within the genome.
mechanisms.
SAFETY AND HANDLING
Handling base analogue mutagens safely is 1. Risk Assessment
crucial due to their potential to cause 2. Personal Protective Equipment
mutations in DNA, which can lead to cancer
3. Engineering Control
and other genetic diseases. Here’s a detailed
4. Safe Work Practices
points on the safety handling of base analogue
5. Emergency Procedures
mutagens:
6. Training and Documentation
CONCLUSION
Base analogue mutagens are powerful
tools for studying genetic processes but
also pose significant risks due to their
I am going to sum up my point with the mutagenic properties. Understanding
statement that.. their mechanisms and effects is crucial for
their safe and effective use in scientific
research.
ANY QUESTION
If you have any question then you can ask for it!

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THANK YOU
FOR YOUR NICE ATTENTION

Hope You Understood Well!