A new study has illuminated an important process that occurs during cell division and is a likely source of DNA damage under some circumstances, including cancer.

The scientists, who reported their findings in Nucleic Acids Research, devised a sophisticated experimental platform for studying the process called «origin licensing.» Cells use this process to regulate, or «license» the replication of their genomes during cell division.

The researchers revealed for the first time the dynamics of this process. They showed in particular how these dynamics differ — and bring different risks of DNA damage during replication — in the two basic states of genomic DNA, the «euchromatin» state which is relatively loose and open for gene activity, and the «heterochromatin» state which is wound more tightly to silence gene activity.

«Our findings may help explain, for example, why certain portions of the genome are relatively susceptible to DNA damage during replication in some cancer cells,» said study senior author Jean Cook, PhD, professor of biochemistry and biophysics at the UNC School of Medicine and member of the UNC Lineberger Comprehensive Cancer Center.

Origin licensing occurs in the initial, preparatory phase of cell replication, known as the G1 phase. It involves sets of special enzymes that attach to the DNA in chromosomes at various locations where DNA-copying is to originate. The enzymes essentially license the copying of DNA so that cells don’t copy their genomes more than once.

Cook and other scientists have described in prior studies the basic process of origin licensing, and have identified proteins that make it happen. But this study, for the first time, revealed in detail how the process unfolds over time in cells as they prepare for cell division. Study first author Liu Mei, PhD, a postdoctoral fellow in the Cook laboratory, combined still and time-lapse microscopic imaging techniques to accomplish this feat.

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