Genomic Instability, Human RecQ Helicases And Homologous Recombination

Main Category: Genetics
Also Included In: Cancer / Oncology
Article Date: 15 Nov 2007 - 3:00 PDT

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Two independent papers in the December 1st issue of G&D detail how human RecQ helicases regulate homologous recombination and protect genome stability.

The human RecQ family of helicases consists of 5 members: WRN, BLM, RECQL4, RECQL1 and RECQL5. These enzymes help to unwind DNA so to facilitate replication, transcription and DNA repair. Mutations in BLM, WRN and RECQ4 cause the cancer-predisposition syndromes Bloom's Syndrome, Werner's Syndrome and Rothmund-Thomson Syndrome, respectively. Interestingly, these cancer-prone genetic conditions are associated with defects in the DNA repair pathway of homologous recombination (HR).

Dr. Alexander Mazin (Drexel University College of Medicine) and colleagues focused their research on the function of the Bloom's syndrome helicase, BLM. They found that BLM has differential roles in regulating HR: depending upon the stage of its involvement, BLM can either promote or inhibit HR -- leading the authors to the surprising conclusion that the "combination of opposing activities gives BLM an important leverage in regulation of HR."

In a separate paper, Drs. Guangbin Luo (Case Western Reserve Univeristy) and Patrick Sung (Yale University School of Medicine) and their colleagues demonstrate that another member of the human RecQ family, RECQL5, can also interfere with HR, by disrupting a particular step (formation of the Rad51 presynaptic filament) in the pathway. Dr. Sung emphasizes that "These results elucidate hoe RECQL5 proetin helps avoid deleterious chromosome rearrangements that can cause tumorigenesis."

Taken together, these papers lend new insight into the molecular function of human RecQ helicases in protecting genome stability and preventing tumorigenesis.

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Source: Heather Cosel
Cold Spring Harbor Laboratory

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