Friday 12 June 2009

Microhomology-mediated End Joining

So I wrote a new article on Wikipedia. It's a little brief but with some collaboration from other internet users it will get better in time.

Microhomology-mediated End Joining

Microhomology-mediated End Joining (MMEJ) is one of the pathways for repairing double-strand breaks in DNA. Two other well known means of double-strand breakage repair are Non-homologous end joining (NHEJ) and Homologous recombination (HR). What distinguishes MMEJ from the other repair mechanisms is the use of 5 - 25 base pair microhomologous sequences to align the broken strands before joining, MMEJ repair is different to NHEJ because it uses a Ku protein and DNA-PK independent repair mechanism and repair occurs during the S phase of the cell cycle as a pose to the G0/G1 and early S phases in NHEJ and late S to G2 phase in HR.

MMEJ works by ligating the mismatched hanging strands of DNA, removing overhanging nucleotides and filling in the missing base pairs. When a break occurs a homology of 5 - 25 complimentary base pairs on both strands is identified and used as a basis for which to align the strands with mismatched ends. Once aligned, any overhanging bases (flaps) and mismatched bases on the strands are removed and any missing nucleotides are inserted. As this method's only way of identifying if the two strands are related is based on microhomology down/up-stream from the site of breakage, it does not identify any missing base pairs which may have been lost during the break and even removes nucleotides (flaps) in order to ligate the strand. MMEJ ligates the DNA strands without checking for consistency and causes deletions since it removes base pairs (flaps) on the strand in order to align the two pieces.

MMEJ is an error-prone method of repair and results in deletion mutations in the genetic code which may initiate the creation of oncogenes that could lead to the development of cancer. In most cases a cell uses MMEJ only when the NHEJ method is unavailable or unsuitable due to the disadvantage posed by introducing deletions into the genetic code.

References

1. http://www.cell.com/trends/genetics/abstract/S0168-9525(08)00229-1 MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings
2. http://nar.oxfordjournals.org/cgi/content/abstract/32/17/5249 DNA double strand break repair in human bladder cancer is error prone and involves microhomology-associated end-joining
3. http://dx.doi.org/10.1016/j.mrfmmm.2007.08.016 Distinctive differences in DNA double-strand break repair between normal urothelial and urothelial carcinoma cells

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