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What do you think the possibility is of a mismatch occurring during the mismatch repair process? What are other functions of DNA polymerase delta?

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One form of DNA damage or aberrant activity is DNA mismatching, which is some form of incorrect nucleotide base pairing. This is something that can occur naturally in processes like DNA replication, without the presence of a pathogenic factor. While the polymerases that facilitate base pairing are typically reliable, there is a level of inherent error that will happen and so the DNA mismatch repair (MMR) system is in place to correct these events. If the cell does not correct these events, gene mutations can occur.

I’ve grabbed a figure depicting the MMR process from Pećina-Šlaus et al. (2020) and pasted it below. The main proteins that are responsible for detecting the mismatch are the MutS alpha and beta proteins. Each version of the MutS protein will detect different types of mismatches.

The MutS protein will scan the DNA until it reaches a mismatch represented here by a kink, which is a result of the maligned conformation of the wrong base pairing. It will then recruit MutL alpha to form a complex by the mismatch. PCNA and RCF will also be recruited, and once this entire complex is formed, the endonuclease activity of MutL alpha will activate to create a strand break by the mismatch.

This strand break is recognized by Exonuclease1 (EXO1), which will target and degrade the mismatch and region around it. DNA polymerase delta will then be recruited to restart proper replication of the DNA segment. Ligase 1 will then join the remaining gap in the formed DNA sequence to complete the repair.

Retrieved from Pećina-Šlaus et al. (2020)

Questions:

What do you think the possibility is of a mismatch occurring during the mismatch repair process? What are other functions of DNA polymerase delta?

Source:

Pećina-Šlaus, N., Kafka, A., Salamon, I., & Bukovac, A. (2020). Mismatch Repair Pathway, Genome Stability and Cancer. Frontiers in Molecular Biosciences, 7. https://doi.org/10.3389/fmolb.2020.00122