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Protein averts cell suicide but might contribute to cancer

research, Fiala developed a new way to sequence very short lengths of DNA. "This allowed us to pin down exactly what mistakes Dpo4 makes," he says.

The findings reveal why the enzyme makes mistakes.

DNA resembles a spiral staircase that is made from separate halves, with half-steps protruding from each. The half-steps fit together down the center to form the complete staircase.

In DNA, the half-steps are known as the bases ?the ‘A's, ‘C's, ‘G's and ‘T's ?that run the length of a DNA helix. A complete step is formed by pairs of bases according to a rule: ‘A' always pairs with ‘T,' and ‘C' always pairs with ‘G.'

When cells make new DNA, the two strands separate, and each old half becomes a template for a new partner. The DNA-making machinery travels along the old half, building the new half according to the bases it finds on the old half. When it meets an ‘A' on the old half, it pairs it with a ‘T' on the new half (and vice versa); when it meets a ‘G' on the old half, it pairs it with a ‘C' on the new strand. In the end, there are two complete DNA molecules instead of one, each made up of an old half and a new half.

But trouble arises during the building if one of the bases ?one of the half steps ?is missing. When the DNA replication machine encounters the gap, it stalls. If the standstill continues, the cell will self-destruct.

It's at this point when Dpo4 jumps in. It adds a base opposite the gap and then leaves, allowing the DNA-making machinery to bypass the damage and continue construction.

The action averts cell suicide, but the gap ?and the stop-gap base ?might become a mutation that, in conjunction with later genetic damage, causes the cell to eventually become cancerous.

"The objective of this enzyme is to allow replication to continue, not to repair the damage," says Fiala. The damage will persist, and cells might try to repair it later. But as long as DNA replication can
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Source:Ohio State University


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