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DNA Repair Mechanisms

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DNA:  Repair Mechanisms (With Diagram)

 The various DNA repair mechanisms are: 1. Direct Repair 2. Excision Repair 3. Mismatch Base Repair 4. Recombination Repair or Retrieval System and 5. SOS Repair Mechanism.

Repair Mechanisms:

Most kinds of damage create impediments to replication or transcription. Altered bases cause mispairing and can cause permanent alteration to DNA sequence after replication.

In order to maintain the integrity of information contained in it, the DNA has various repair mechanisms.

1. Direct Repair:

The damage is reversed by a repair enzyme which is called photoreactivation. This mechanism involves a light dependant enzyme called DNA photolyase. The enzyme is present in almost all cells from bacteria to animals. It uses energy from the absorbed light to cleave the C-C bond of cyclobutyl ring of the thymine dimers. In this way thymine dimers are monomerized.

2. Excision Repair:

It includes base excision repair and nucleotide excision repair. Base excision repair system involves an enzyme called N-glycosylase which recognizes the abnormal base and hydrolyes glycosidic bond between it and sugar.

Another enzyme, an endonuclease cleaves the DNA backbone on the 5′-side of the abnormal base. Then the DNA polymerase by its exonuclease activity removes the abnormal base. DNA polymerase then replaces it with normal base and DNA ligase seals the region.

Nucleotide repair system includes three steps, incision, excision and synthesis. Incision is done by endonuclease enzyme precisely on either side of the damaged patch of the strand. In this way damaged portion of the strand is cleaved.

Endonuclease enzymes involved are UvrA, UvrB which recognize the damaged stretch of the strand. UvrC makes two cuts (incision) on either side. Exonuclease removes the damaged strand. Enzyme involved is UvrD.

Later, DNA polymerase synthesizes the new strand by using complementary strand as a template. DNA ligase forms phosphodiester bonds which seal the ends on newly synthesized strand.

3. Mismatch Base Repair:

Sometimes wrong bases are incorporated during replication process, G-T or C-A pairs are formed. The wrong base is always incorporated in the daughter strand only. Therefore in order to distinguish the two strands for the purpose of repair, the adenine bases of the template strand are labelled or tagged by methyl groups. In this way the newly replication DNA helix is hemimethylated. The excision of wrong bases occur in the non-methylated or daughter strand.

4. Recombination Repair or Retrieval System:

In thymine dimer or other type of damage, DNA replication cannot proceed properly. A gap opposite to thymine dimer is left in the newly synthesized daughter strand. The gap is repaired by recombination mechanism or retrieval mechanism called also sister strand exchange.

During replication of DNA two identical copies are produced. Replicating DNA molecule has four strands A, B, C and D. Strands A and C have same DNA , sequence. Strands B and D also have same sequence as they are identical. A thymine dimer is present in strand A. The replication fork passes the dimmer as it cannot form hydrogen bonds with incoming adenine bases, thus creating a gap in the newly synthesized strand B.

In recombination repair system a short identical segment of DNA is retrieved from strand D and is inserted into the gap of strand B. But this creates a gap in strand D which is easily filled up by DNA polymerase using normal strand C as a template. This event is dependent on the activity of a special protein Rec A. The Rec A protein plays its role in retrieving a portion of the complementary strand from other side of the replication fork to fill the gap. Rec A is a strand exchange protein.

After filling both gaps, thymine is monomerised. So in this repair mechanism a portion of DNA strand is retrieved from the normal homologous DNA segment. This is also known as daughter strand gap repair mechanism.

5. SOS Repair Mechanism:

Sometimes the replicating machinery is unable to repair the damaged portion and bypasses the damaged site. This is known as translesion synthesis also called bypass system and is emergency repair system. This mechanism is catalyzed by a special class of DNA polymerases called Y-family of DNA polymerases which synthesized DNA directly across the damaged portion.

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