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DNA repair against gene amplification

 
  July, 12 2001 7:38
your information resource in human molecular genetics
 
     
Gene amplification, a process leading to an increase in the copy number of a portion of the genome, is one of the hallmarks of the genomic instability frequently encountered in neoplastic cells. Whereas it has never been detected in somatic cells, amplification of proto-oncogenes was observed in several types of solid tumors, underlying a possible role for gene amplification in tumorigenesis.

DNA double strand breaks (DSB) are thought to trigger gene amplification, probably through the activation of repair pathways. In mammalian cells, the main mechanism involved in the DSB repair is the non-homologous end-joining pathway (NHEJ). In a recent issue of Cancer Research, Mondello et al. show that the probability of gene amplification is increased in the absence of DNA-PK, one of the proteins central to the NHEJ pathway (Cancer Research 61, 4520-4525, June 1, 2001). However, this was only observed in the permissive genetic backgroud of immortalized cells, thus placing gene amplification downstream of some primary events occurring in a multiple step cancer development. These results further underline the importance of proteins involved in the NHEJ pathway in maintaining genome integrity.


CONTACT

Chiara Mondello
phone 39-0382-546332
fax 39-0382-422286
e-mail mondello@igbe.pv.cnr.it


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