New paper by the Cejka Lab
on Friday, March 24, 2017
The laboratory of Prof. Cejka studies how cells repair damaged or broken DNA. DNA can break as a result of exposure to radiation, chemicals or errors during natural cellular processes such as DNA replication. A failure to repair broken DNA may result in cell death, while incorrect repair may give rise to mutations and cancer. To repair DNA breaks without introducing mutations, cell employ a process termed homologous recombination. The first step in the recombination pathway involves a processing of the broken DNA end to make it suitable for repair. In a new paper that will be published in Genes and Development on March 23rd, 2017, Dr. Cejka and colleagues describe the function of one of the proteins that is involved in the initial DNA end processing. This factor, termed Dna2, can both degrade DNA as well as separate the two strands of the DNA helix. "We discovered that Dna2 is a fascinating molecular machine, which combines several activities to optimally prepare DNA for the recombination pathway", Cejka describes his work. A number of anti cancer regimens including radiotherapy and diverse chemotherapeutic drugs kill cancer cells by inducing DNA breaks. Detailed understanding of the DNA repair process may give rise to novel or improve existing therapeutic strategies in the future.
Model for the involvement of yDna2 helicase activity in DNA end resection. (A) Sgs1 translocates on the 3′-terminated DNA strand and functions as the lead helicase. Yeast Dna2 is using its motor activity to translocate on the unwound 5′-terminated DNA strand, which is degraded by its nuclease activity. (B, top) The motor of yDna2 accelerates degradation of ssDNA, which requires ATP hydrolysis and the presence of yRPA. This fast mode of DNA degradation results in long DNA degradation fragments. (Bottom) Without active translocation, the ssDNA degradation by yDna2 is slow, resulting in short DNA degradation fragments.
The motor activity of DNA2 functions as an ssDNA translocase to promote DNA end resection, Maryna Levikova, Cosimo Pinto and Petr Cejka
Genes Dev. Published in Advance March 23, 2017, doi:10.1101/gad.295196.116