Alkylating chemicals like nitrosamines and mustard gas can transfer methyl or ethyl groups to DNA bases and backbone phosphates. One vulnerable site is the keto group on guanine 6, where methylation causes guanine to pair with thymine instead of cytosine during replication, changing a G-C pair to an A-T pair. Cells use DNA damage response and repair mechanisms like direct repair, excision repair, and error-prone repair to preserve genome integrity against endogenous and exogenous DNA damage. Defects in repair pathways can cause inherited human diseases.

13. In alkylation, methyl or ethyl groups are transferred
to reactive sites on the bases and to phosphates in
the DNA backbone.
Alkylating chemicals include:
• nitrosamines
• Mustard gas.
One of the most vulnerable sites of alkylation is the
keto group at carbon atom6 of guanine. The
product of this methylation, O6-methylguanine,
often mispairs with thymine, resulting in the
change of a G:C base pair into an A:T base pair
when the damaged DNA is replicated.
Alkylation

21. DNA – REPAIR MECHANISM

23. Preservation of genome integrity
is an essential process for cell
homeostasis. During the course
of life of a single cell, the genome
is constantly damaged by
endogenous and exogenous
agents. To ensure genome
stability, cells use a global
signalling network, namely the
DNA damage response (DDR) to
sense and repair DNA damage.
DDR senses different types of
DNA damage and coordinates a
response that includes activation
of transcription, cell cycle
control, DNA repair pathways,
apoptosis, senescence, and cell
death.

24. TYPES OF DNA REPAIR MECHANISM :
A) DIRECT REPAIR
 Repair by DNA polymerase proofreading
 Light dependent repair
 Repair of alkylation damage
B) REPAIR INVOLVING EXCISION
 Nucleotide excision repair
 Base excision repair
 Mismatch repair
C) ERROR PRONE
 SOS/ Translesion Repair
 Homologous Recombination
 Non-Homologous Recombination

40. MODE OF ACTION

42. Inherited Human Diseases with Defects in DNA Repair