Navigation Links
DNA mutation rates raise curtain on cause of cancer
Date:7/1/2010

Waltham, MAWhat if we could understand why cancer develops? We know that certain risk factors, such as smoking or excessive sun exposure, can increase the chances of developing this terrible disease, but cancer can form in any tissue, and the cause is not always clear. One idea that has emerged is that for a cell to transform into a cancer cell it must suffer a large number of mutations affecting different genes needed to control cell growth. In a study published this week in Science, Brandeis University researchers have found that the process of repairing DNA damage also unexpectedly increases the rate of mutations and changes the kinds of mutations that arise.

Surprisingly, as cells progress toward full-blown cancer they begin to suffer alterations of the normal DNA replication process, leading to an increased amount of DNA damage, especially chromosome breaks. Thus there is an increased need for cells to accurately repair these breaks.

Biologist James Haber, graduate student Wade Hicks and undergraduate Minlee Kim report that the repair of damaged strands of DNA, specifically by a process known as gene conversion, can cause higher-than-normal levels of mutation; in fact, 1,400 times as high as spontaneous mutations in cells.

"It has been hard to imagine how cells could accumulate so many mutations in the few generations that they undergo cell division on the way to becoming cancerous," Haber said. "We think that the elevated rate of mutation at sites where DNA has been broken may be an important source of these gene changes."

Most DNA damage takes the form of double-stranded DNA breaks (DSBs), for which the cell has multiple methods of self-repair. One method, gene conversion (GC), was originally believed to be relatively error-free, since it involves repairing the break by copying in DNA from a nearly identical sequence that serves as a library to restore the original DNA sequence.

"During repair, mutation rates increase, and the types of mutation during repair are different from normal mutagenesis, explained Hicks, the lead author. "It would be interesting to do an in depth analysis of the types of mutations in cancer cells and compare to those we observed in a repair event to see if they match up."

While other studies have looked at GCs and mutation rates in the past, this is the first study to look directly at the region where both DNA strands are replaced. The researchers used yeast cells, a simple organism in which it is possible to induce a single DSB at one location in all cells and then count the number of mutations that arise during the repair of the break. Through this simple system, Haber and his colleagues were able not only to measure the mutation rates, but also to determine which DNA repair enzymes are most important for GC, and to suggest a possible reason for the high number of mutations created.

They discovered that an innate repair system known as mismatch repair does not get recruited during GC; therefore mutations cannot be fixed. In addition, they discovered that many of the repair-associated mutations had a distinct "signature", which suggested that the copying of DNA that must occur during the repair of the break was frequently interrupted and required a way to "find the right place" to recommence copying. One striking consequence of the lack of straightforward copying was that some of the repair events involved "template switches," in which the copying machinery jumped from the template it was supposed to use to another, distantly related DNA sequence on another chromosome.

"The next steps for this project will be to better characterize these template switches we observed," said Hicks. "What is the actual rate of these events? What proteins are required or not to do the template switches?"

It will now be important to see if there is an acceleration of mutagenesis in precancerous mammalian cells and to learn if there are ways to prevent it from occurring.


'/>"/>

Contact: Laura Gardner
gardner@brandeis.edu
781-736-4204
Brandeis University
Source:Eurekalert

Related medicine news :

1. Gene Mutations Behind Brain Reduction
2. Single gene mutation induces endometrial cancer
3. Genetic Mutation Linked to Prostate Cancer in Blacks
4. Gene Mutations Identified for Charcot-Marie-Tooth Syndrome
5. Study shows that mutations in 1 gene cause many cancers
6. Parkinsons Linked to Genetic Mutation
7. Breast cancer patients with BRCA mutations 4 times more likely to get cancer in opposite breast
8. Gene Mutations Up Risk for Cancer in Opposite Breast
9. Gene Mutation Ups Risk of Sudden Death in People with Epilepsy
10. Heart Disease Among Childhood Cancer Survivors Tied to Gene Mutations
11. New research indicates that DNA sequence itself influences mutation rate
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/10/2016)... ... February 10, 2016 , ... LaserShip, a regional parcel carrier that services the ... Eastern Michigan last Friday in order to aid in the Flint water crisis. In ... a facility located in Clio, only 15 miles away from Flint. , “We have ...
(Date:2/10/2016)... ... February 10, 2016 , ... InDemand ... within Healthcare, recently partnered with Heart City Health Center to improve ... 23 years, Heart City Health Center has provided the Elkhart community with access ...
(Date:2/10/2016)... (PRWEB) , ... February 10, 2016 , ... 10 ... Brand. There were three leading bottled water brand owners that topped the list as ... enhance connectivity and optimize conversion. The premier brand was Tibet 5100, a top notch ...
(Date:2/10/2016)... ... February 10, 2016 , ... ... welcomes S.S. Nesbitt as the latest addition to its growing list of Partner ... locations throughout the Southeast, from Orlando to Huntsville and in between. , Harnessing ...
(Date:2/10/2016)... ... February 10, 2016 , ... Pediatric therapists are challenged to ... shows that the Goal Attainment Scale (GAS) captures 20% more change in outcomes ... more about the Goal Attainment Scale, Education Resources Inc. is offering a course ...
Breaking Medicine News(10 mins):
(Date:2/10/2016)... and PITTSBURGH, Feb. 10, 2016 Mylan N.V. (NASDAQ, ... quarter and year ended December 31, 2015. ... Full year adjusted total revenues of $9.45 billion, up ... year; GAAP total revenues of $9.43 billion. Excluding the ... markets specialty and branded generics business (the "EPD Business"), ...
(Date:2/10/2016)... , Feb. 10, 2016  Resolve Therapeutics, ... transformative new approaches to the treatment of lupus ... of a multiple ascending dose study in patients ... compound RSLV-132. --> ... placebo-controlled multiple ascending dose study of RSLV-132 in ...
(Date:2/10/2016)... , Feb. 10, 2016  Rich Pharmaceuticals, Inc. (OTC ... a 1-for-100 reverse split of its issued and outstanding ... trading on Thursday, February 11, 2016. The Company,s common ... CUSIP number 76303T308 and temporary ticker symbol "RCHAD". After ... under the ticker symbol (RCHA).  --> ...
Breaking Medicine Technology: