Navigation Links
Protein averts cell suicide but might contribute to cancer

Scientists have discovered how an unusual protein helps a cell bypass damage when making new DNA, thereby averting the cell's self-destruction.

But they also discovered that this protein, an enzyme called Dpo4, often makes errors when copying the genomic DNA sequence that later might cause the cell to become cancerous.

The findings by researchers with Ohio State University 's Comprehensive Cancer Center are described in two back-to-back papers in The Journal of Biological Chemistry.

"Unrepaired DNA damage presents a big roadblock for the DNA replication machinery, which cannot go around it," says Zucai Suo, assistant professor of biochemistry. "This damage will trigger cell death because the DNA is not replicated.

"This protein bypasses the damage and saves cells from self-destructing, but it is very error prone, which suggests that it may also play a role in cancer."

Dpo4 is one of a family of enzymes called Y-family DNA polymerases that were first discovered about 10 years ago and are only now becoming understood.

"These enzymes provide a survival mechanism for cells," says first author Kevin Fiala, a graduate student in Suo's laboratory. "They allow DNA replication to continue, so the cell doesn't die. But they don't repair the DNA damage that exists."

DNA damage is a routine problem for cells, Suo says. For example, every cell loses more than 10,000 DNA bases daily. Dedicated repair enzymes fix 80 percent or more of this damage, but the rest remains.

Cells use Y-family enzymes to bypass that remaining damage when making new DNA prior to cell division, thus forcing these enzymes to copy damaged DNA.

How these bypass enzymes work, however, isn't known. The Dpo4 protein used in this research comes from a microorganism. It is relatively easy to produce in large quantities and to study, and it is similar to one of the four such enzymes found in humans.

For this 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 continue, the cell survives."

Currently, Suo's laboratory is investigating human Y-family DNA polymerases.

Source:Ohio State University

Related biology news :

1. Quantum Dots Research Leads to New Knowledge about Protein Binding in Plants
2. Protein discovery could unlock the secret to better TB treatment
3. Researchers Uncover Key Step In Manufacture of Memory Protein
4. An HIV Protein Plays a Surprising Role in Gene Activation
5. Protein Packages Found To Activate Genes; May Be What Regulates Development And Disease
6. New SARS Protein Linked To Important Cell Doorway
7. The Shapes Of Life: NIGMS Project Yields More Than 1,000 Protein Structures
8. PANTHER Protein Classification System Database 5.0
9. Duke Chemists Isolating Individual Molecules Of Toxic Protein In Alzheimers, Parkinsons Disease
10. Newly Discovered Compound Blocks Known Cancer-Causing Protein
11. UF Researchers Map Bacterial Proteins That Cause Tooth Loss

Post Your Comments:

(Date:11/4/2015)... , November 4, 2015 ... market report published by Transparency Market Research "Home Security Solutions ... and Forecast 2015 - 2022", the global home security solutions ... bn by 2022. The market is estimated to expand ... from 2015 to 2022. Rising security needs among customers ...
(Date:10/29/2015)... 2015   MedNet Solutions , an innovative SaaS-based ... clinical research, is pleased to announce that it has ... as one of only three finalists for a ... and Growing" category. The Tekne Awards honor Minnesota ... technology innovation and leadership. iMedNet™ eClinical ...
(Date:10/29/2015)... Va. , Oct. 29, 2015 Daon, ... today that it has released a new version of ... customers in North America have ... IdentityX v4.0 also includes a FIDO UAF certified ... are already preparing to activate FIDO features. These customers ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , Nov. 25, 2015 /PRNewswire/ - Aeterna Zentaris ... that its business and prospects remain fundamentally strong ... Zoptrex™ (zoptarelin doxorubicin) recently received DSMB recommendation to ... completion following review of the final interim efficacy ... 2 Primary Endpoint in men with heavily pretreated ...
(Date:11/25/2015)... PORTLAND, Oregon , November 25, 2015 /PRNewswire/ ... Deep Market Research Report is a professional and ... Genomics industry.      (Logo: ... basic overview of the industry including definitions, classifications, ... analysis is provided for the international markets including ...
(Date:11/24/2015)... ... 24, 2015 , ... The United States Golf Association (USGA) today announced Dr. ... Award. Presented annually since 1961, the USGA Green Section Award recognizes an individual’s distinguished ... , Clarke, of Iselin, N.J., is an extension specialist of turfgrass pathology in ...
(Date:11/24/2015)... VANCOUVER , Nov. 24, 2015 /CNW/ - iCo ... ICOTF), today reported financial results for the quarter ... are expressed in Canadian dollars and presented under ... the United States ," said Andrew ... "These advancements regarding iCo-008 are not only value ...
Breaking Biology Technology: