Mismatches and bubbles in DNA
Yan Zeng 1 and Giovanni Zocchi 2*
1 UCLA
2 University of California - Los Angeles
* To whom correspondence should be addressed. E-mail: zocchi{at}physics.ucla.edu.
Submitted on June 29, 2005
Revised on August 2, 2005
Accepted on 3 February 2006
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Abstract |
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Single mismatches in the DNA double helix form nucleation sites for bubbles. While the overall melting temperature of the duplex is affected to different degrees depending on the probe length, the statistical weights of the bubble states around the defect are always strongly affected. Here we show experimentally that a single mismatch has indeed a dramatic effect on the distribution of intermediate (bubble) states in the melting transition of DNA oligomers. For probe lengths in the range 20 to 40 bases, the mismatch transforms a transition with many intermediates into a nearly two-state transition. One surprising consequence is the existence of a regime where the sensitivity of a mismatch detection assay based on monitoring intermediate states would increase with probe length. Our results provide experimental constraints on how mismatches should be implemented in models of DNA melting, such as the widely used thermodynamic nearest neighbor model, to which we compare our data.
Key Words:
DNA melting, intermediate states, single mismatch