Detect & Recognize

Restore

Remove

DNA Repair

=

DNA Integrity

DNA repair systems follow the same mechanistic outline: 1.Recognize (Detect) the inappropriate base(s).

2.Remove (Excise) the inappropriate base(s).

3.Fill (Restore) in the resulting gap with DNA polymerase I and DNA ligase.

Base damage-based DNA Repair

Exonuclease vs Endonuclease

Excision vs Incision

How many bases? 1 base Base-excision repair Over 1 (multiple) bases Nucleotide-excision repair

Repair Excise lesion : Nuclease Gap-filling :DNA polymerase Sealing :DNA ligase

Detection

Repair

http://www.youtube.com/watch?v=q_c-2APr-cE

1. Detection[Structural & Chemical]

1 damaged-base 2. Remove Remove of the damaged-base 3. Incision for marking Nick to the DNA backbone 4. Excision for removing Cleavage of the other backbone 5. Gap-filling Sequence-based replication 6. Link of the ends ligation of the nucleotide ends

Base-excision repairbase modification

Working protein (enzyme)

http://www.hhmi.org/biointeractive/mismatch-repair

1. Detection[Structural & Chemical]

1 damaged-base 2. Incision for marking Nick to the DNA backbone 3. Excision for removing Cleavage of the other backbone 4. Gap-filling Sequence-based replication 5. Link of the ends ligation of the nucleotide ends

Mismatch repairerror in the replication process

How does the repair system know which base is incorrect?

5’-methylation

Misincorporation in the replication

Identification before detection

If not corrected, genetic information changes by GT

Chemical modification of base

Adenine methylation =Marker

Treating of common mutation

http://www.youtube.com/watch?v=rYreAcn04-M

1. Detection[Structural]

Over 1 damaged-base 2. Remove by Excision Remove of the damaged-base 3. Gap-filling Sequence-based replication 4. Link of the ends ligation of the nucleotide ends

Nucleotide-excision repair Working protein (enzyme)

The nucleotide-excision repair system recognizes structural distortion in the DNA double helix

What are the COMMON things through them?

A: DNA’s property of being a double helix. Damage to one strand of DNA can

be repaired by the use of the other strand as a template.

The Damage can be repaired DIRECTLY

1. Detection[Structural]

Over 1 damaged-base 2. Remove by Cleavage Remove of the damaged-base

Direct repair

DNA photolyase

Deaminationspontaneous

5’-methylation

Why is the thymine employed in DNA?

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Thymidine is used in DNA instead of uracil, which also pairs with adenine, to preserve the integrity of the genetic information. Cytosine spontaneously deaminates to form uracil. If uracil naturally occurred as a base in DNA, cytosine deamination would lead an A-U pair replacing a G-C pair after the next round of replication. Use of thymidine instead of uracil allows the detection of deamination of cytosine. If uracil is detected in DNA, it is removed by uracil DNA glycosylase and the resulting AP is repaired with the insertion of cytosine.

Various types of the DNA damage

?

Single-strand break

How double-strand break happens?

Double-strand breaks can be repaired by Recombination

Detect & Recognize

Restore

Remove

Recombination Repair

=

DNA Integrity

http://www.youtube.com/watch?v=3qgBKrAZCLg

http://www.youtube.com/watch?v=JOL6YF3Wifs

1. Detection[Structural]

Double-strand break 2. Single-stranded DNA generation Preparation for the DNA synthesis 3. Strand invasion Complementary base-paring 4. DNA replication Complementary duplication 5. Junction cleavage & ligation Recombination generation 6. DNA repair

Homologous DNA recombination

4:22

Recombination is a complicated process requiring dozens of proteins. 1.The double strand break is recognized and the 5’ ends are digested generating single-strand regions that are bound by RAD51.

2.Strand invasion occurs when a single strand from the damaged DNA replaces a strand in the undamaged DNA. The resulting three-stranded structure is called a displacement loop.

3. DNA synthesis occurs, using the undamaged DNA as a template.

4.A second strand invasion occurs to complete the repair, forming a structure called a Holliday junction.

5. Cleavage and ligation yield two intact helices, and as a result recombination generates.

A: DNA’s property of being a double helix. Damage to one strand of DNA can

be repaired by the use of the other strand as a template.

So, can you recognize such the various damages on the DNA double helix?