A diversity of DNA lesions= A diversity of DNA repair mechanisms
Genotoxic agents include: UV, PAHs, oxidative stress, ionizing radiations, drugs etc.

1. Base Excision Repair>>> BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases, forming AP sites. These are then cleaved by an AP endonuclease. The resulting single-strand break can then be processed by either short-patch (where a single nucleotide is replaced) or long-patch BER (where 2-10 new nucleotides are synthesized).

2. Nucleotide Excision Repair

3. Mismatch Repair

*3 pathways share common « cut and paste » mechanisms (excision/synthesis)

4. Direct Reversion

5. Recombination (HR & NHEJ)

Homologous Recombination=
1. Repairs DNA before cell enters M phase
shortly after DNA replication in S and G2 phase where sister chromatids are easily visible

2. Homologous sequence required to guide repair

3. Requires homologous sequences/chromosomes ;
Two primary models: DSBR pathway= double holiday junction model and SDSA= synthesis dependant strand annealing pathway

4. Inappropriate HR leads to production of CABS>>> which are involved in carcinogenesis

Non-Homologous End Joining (NHEJ)

1. Predominant in G1 phase, when cells are growing but not yet ready to divide, (less frequent after G1 but maintains some activity through out the cell cycle)

2. The break ends are directly ligated without the need for homologous template

3. Utilizes short homologous DNA sequences called 'microhomologies' often present in single stranded overhangs on the ends of dsb's

4. Inappropriate NHEJ can lead to translocation and telomere fusion>>> hallmarks of cancer

	Created by rabab594 about 10 years ago

Note on Untitled, created by rabab594 on 29/03/2014.

Untitled