Genome complexity: Enzymes repair DNA copy mistakes (Introduction)

by David Turell , Tuesday, October 25, 2016, 18:47 (2739 days ago) @ David Turell

DNA is constantly copied and mistakes occur. Enzymes are found to facilitate quick repair:

http://phys.org/news/2016-10-key-dna-replication-protein.html

"PrimPol is used in cells when normal repair proteins encounter damaged sections of DNA, often caused by anticancer chemotherapy drugs. The protein can skip over the damage to rescue DNA replication, says the study's senior investigator, Aneel K. Aggarwal, PhD, Professor of Pharmacological and Oncological Sciences at ISMMS

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"DNA damage happens constantly—more than 100,000 events occur in every human cell each day. PrimPol is necessary for the cell to repair DNA damage, but sometimes this may not be to the individual's benefit, as in the case of resistance to chemotherapeutic agents, says the study's co-lead author, Olga Rechkoblit, PhD, Assistant Professor of Pharmacological Sciences at ISMMS.

"The basic steps involved in DNA replication are known. The first step involves unzipping the intertwined double helix DNA structure, creating a "Y" shape known as a replication fork. These two strands act as templates for making the new DNA strands. A short piece of RNA known as a primer (produced by a primase enzyme) acts as the starting point for the synthesis of new DNA.

"'It had been believed that DNA polymerase and primase activities in human cells were the province of separate enzymes. Then PrimPol was discovered, and the understanding of DNA replication changed dramatically. PrimPol was found to be capable of both restarting and performing DNA synthesis after DNA replication stalls," says Dr. Rechkoblit.

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"While scientists were excited by the discovery of the enzyme, they didn't understand how it worked. Drs. Aggarwal and Rechkoblit organized a team of investigators from Cornell University in New York, Argonne National Laboratory in Illinois, and the University of Texas Medical Branch in Galveston to find out.

"'Because the three-dimensional structure of the enzyme is so different from that of other DNA polymerases, it required a group effort to elucidate its structure," says Dr. Aggarwal.

"The clinical implications are clear, Dr. Rechkoblit says.

"Many chemotherapy agents kill cancer cells by damaging their DNA and preventing the completion of DNA replication. PrimPol, on the other hand, promotes the replication progression and, thus, cell survival," she says. "Knowing the structure of PrimPol described in the current study is invaluable for designing an inhibitor for this enzyme as a future cancer therapy."

The actual structure of the enzyme is shown at this site:

http://advances.sciencemag.org/content/2/10/e1601317.full

Comment; Without copy corrections life could not survive. This huge enzyme is necessary at the beginning of life. God must have given it. considering its size and complexity.