DNA REPAIR MECHANISMS

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BASE-PAIR
MISMATCH

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• Base pair mismatch occur during
DNA replication.
• There are DNA repair mechanisms
that can fix such mistakes.
• One such mechanism is “Methyl-
Directed Mismatch repair
mechanism”.

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Methyl-Directed
Mismatch Repair
Mechanism in E.coli

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• This mechanism relies on the fact
that methylation of a newly
synthesized DNA strand does not
occur until a short period (a few
seconds-minutes).
• This transient unmethylated state
of newly synthesized strand
permits the new strand to be
distinguished from the template
strand(parent strand).

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MECHANISM
• Three proteins: Mut S
Mut L
Mut H
• Mut S detects the mismatch site &
binds to it.
• Mut S forms a complex with Mut L.
• The formation of Mut S-Mut L
complex recruits Mut H to GATC
sequence at hemimetylated site.

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• Mut S- Mut L complex interacts
with Mut H by a DNA-looping
mechanism.
• Mut H has a site-specific
endonuclease activity that is
inactive until the complex
encounters a hemimethylated
GATC sequence.
• At this site, Mut H catalyzes the
cleavage of the unmethylated
strand on 5’ side of G in GATC.

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If the mismatch is on the 5’side
of the cleavage site….
• the unmethylated strand is
unwound and degraded in the 3’-5’
direction from the cleavage site
through the mismatch.
• This segment is replaced with new
DNA with the combined action of
DNA helicase II, SSB,
exonuclease I,DNA polymerase III,
and DNA ligase.

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When the mismatch is on the
3’side of the cleavage site…
• The pathway is similar except that
the exonuclease is either
exonuclease VII (which degrades
single stranded DNA in the 5’-3’ or
3’-5’direction) or RecJ nuclease
(which degrades single-stranded
DNA in the 5’-3’direction)

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• This mechanism preserves the
base pairing that was present in
the original DNA molecule.

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THANKS