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Human RecQ Helicases, Homologous Recombination and Genomic Instability

11/14/2007

Human RecQ Helicases, Homologous Recombination & Genomic Instability

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.


Identification of a Novel Class of (Not-So) Small RNAs


In the December 1st issue of G&D, Dr. Hailing Jin and colleagues (UC Riverside) report on their discovery of a new class of small RNAs in Arabidopsis. These newly-discovered, 30-40 nt long small RNAs have been dubbed “long short interfering RNAs (lsiRNAs),” and are induced by bacterial infection or under specific growth conditions. While liRNAs share some hallmark features with other, previously identified classes of plant small RNAs, there are also some important differences: In addition to their relatively large size, lsiRNAs have unique biogenesis and target degradation pathways. Dr. Jin adds that “Our study suggests that small RNA families and small RNA-mediated gene regulation are far more diverse and complex than we expected. These novel lsiRNAs may play important roles in host immunity.”


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