DNA repair mechanism

Contents

Introduction

Sources of damage

Types of repair mechanisms

DNA repair and aging

DNA repair and cancer

References               

Introduction

          DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome.

Sources of damage

Endogenous damage:

Spontaneous mutation

Oxidative deamination

Exogenous damage:

Ultraviolet [UV 200-300nm] radiation

X-rays and Gamma rays

Plant toxins

Mutagenic chemicals

Chemotherapy and Radiotherapy

Types of repair

Preventative

Direct DNA repair

Post replication repair

Preventative repair

Eliminate superoxide free radicals

Direct DNA repair

Mainly three types:

Alkyltransferase

Photoreactivation

Excision repair

Alkyltransferases

A group of enzymes which remove alkyl group from the bases of DNA

The best studied of the alkyltransferase is O6 – methyl guanine methyl transferase (MGMT).

Photoreactivation

Restores dimerized pyrimidines to their original form

Excision Repair

Recognizes and excises damaged nucleotides and arrange them with the correct ones

Postreplication repair

There are mainly three types:

Recombination repair

Mismatch repair

SOS response

Recombination repair

Replaces a lesions with the addition of correct nucleotides using one strand as a template

Mismatch repair system

Replaces mismatched nucleotides with the correct one

SOS responses

Activate excision, recombination and other response mechanisms

DNA repair and aging

DNA repair and cancer

Inherited mutations that affect DNA repair genes are strongly associated with high cancer risks in humans.

Hereditary nonpolyposis colorectal cancer (HNPCC) is strongly associated with specific mutations in the DNA mismatch repair pathway.

BRCA1 and BRCA2, two famous mutations conferring a hugely increased risk of breast cancer on carriers, are both associated with a large number of DNA repair pathways.

DNA bases may be modified by deamination OR alkylation.
The position of the modified (damaged) base is called the ‘abasic site’ or ‘AP site’
In the E.coli the DNA glycolsylase can recognize the AP site and remove its bases.

Then the AP endonuclease removes the AP site and neighbouring nucleotides.

The Gap is filled by DNA polymerase I and DNA ligase.


NUCLEOTIDE EXCISION REPAIR

In E.coli proteins UvrA, UvrB, UvrC are involved in removing the damaged nucleotides.
The gap is then filled by DNA polymerase I and DNA ligase.
Nucleotide excision repair is particularly important in recongnising thymine dimers that form as a result of exposure to UV radiation.

MISMATCH REPAIR

To repair mismatched bases the system has to know which base is the correct one.
In E.coli this is achieved by a special methylase called “Dam methylase”, which can methylate all adenines that occur within (5’) GATC sequence.
To distinguish old and new strand old strand is methylated while new is not.

CONCLUSION

DNA repair mechanisms promote genomic stability and prevent cancer.
Thus, DNA repair mechanisms provide a way of proofreading and repairing damaged DNA.

References

Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. (2004). Molecular Biology of the Cell, p963. WH Freeman: New York, NY. 5th ed.

Toshihiro Ohta, Shin-ichi Tokishita, Kayo Mochizuki, Jun Kawase

Masahide Sakahira and Hideo Yamagata, UV Sensitivity and Mutagenesis of the Extremely Thermophilic Eubacterium Thermus thermophilus HB27, Genes and Environment Vol. 28 (2006) , No. 2 p.56-61.

Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R. (2004). Molecular Biology of the Gene, ch. 9 and 10. Peason Benjamin Cummings; CSHL Press. 5th ed.