Environmental Factor

August 2011


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Mutation cluster discovery wins postdoc Roberts a poster prize

By Eddy Ball
August 2011

Steven Roberts, Ph.D.

Roberts also received a number of honors during his undergraduate years at Bowling Green State University, and in his graduate program in biochemistry and biophysics at UNC-CH. He has received several scholarships and, in 2003, was inducted into the Phi Beta Kappa Honor Society. (Photo courtesy of Steve McCaw)

NIEHS postdoctoral fellow Steven Roberts, Ph.D.(http://www.niehs.nih.gov/research/atniehs/labs/lmg/cs/staff.cfm), added yet another award to his list of honors with a best poster win at the 2011 Gordon Research Conference (GRC) on Genetic Toxicology. Roberts presented research he conducted with members of the NIEHS Laboratory of Molecular Genetics (LMG) Chromosome Stability Group and colleagues at the University of North Carolina at Chapel Hill (UNC-CH), titled “Damage-Induced Localized Hypermutability at Double-Strand Breaks and Replication Forks.”

In her message of congratulations, Cell Press Marketing/Publicity Coordinator Mary Beth O'Leary told Roberts he would receive a complimentary subscription to the journal Molecular Cell, sponsor of the poster competition. Cell Press also congratulated Roberts July 24 on its Facebook page and at CellPressNews on Twitter(http://twitter.com/#!/cellpressnews) Exit NIEHS.

Held July 10-15 in Barga, Italy, the conference also featured oral presentations by one of Roberts' mentors, Principal Investigator Michael Resnick, Ph.D.(http://www.niehs.nih.gov/research/atniehs/labs/lmg/cs/index.cfm); Laboratory of Structural Biology (LSB) Chief and LMG Principal Investigator Thomas Kunkel, Ph.D.(http://www.niehs.nih.gov/research/atniehs/labs/lmg/dnarf/index.cfm); and LSB DNA Repair and Nucleic Acid Enzymology Group Principal Investigator Samuel Wilson, M.D.http://www.niehs.nih.gov/research/atniehs/labs/lsb/dnarna/index.cfm Joining them as presenters was former LMG Principal Investigator Ben Van Houten, Ph.D., who is now at the University of Pittsburgh, and other leading authorities in genetic toxicology.

Surprising discovery of large mutation clusters

According to Roberts, his team's poster depicted work showing that chronic exposure of mitotic yeast to low levels of a DNA damaging agent results in the formation of large mutation clusters. Since mutations are traditionally perceived as random independent events, the investigators said they were surprised to discover these large mutation clusters, which contain as many as 30 simultaneous mutations and stretch across some 250 kilobases.

The team found that these clusters are targeted to areas of persistent single-strand (ss) DNA associated with DNA double-strand break repair and replication fork dysfunction. These ssDNAs accumulate DNA lesions that cannot be repaired and are subsequently converted to mutations by error-prone translesion synthesis.

“This is an important advance in the field as the simultaneous generation of mutations amplifies the number of tracks by which genetic changes may accumulate during evolution and in the onset of genetic disease,” Roberts explained. “Our work is the first to link the generation of mutation clusters to specific cellular processes like homologous recombination and replication.”

Shaping a career while training at NIEHS

Roberts joined NIEHS as an Intramural Research Training Award fellow following completion of his doctorate at UNC-CH in 2008. Since then his has co-authored two publications, participated in five poster competitions, and delivered two invited talks at conferences. He has served as an NIEHS Summer Internship Program mentor and an Undergraduate Research Program mentor. Roberts is a former LMG Trainee Action Committee representative and served as host for an LMG Fellows Invited Lecture Series presentation May 2 by cancer biologist Roger Greenberg, M.D., Ph.D. (see story(http://www.niehs.nih.gov/news/newsletter/2011/june/science-lmg/index.cfm))

In addition to his win at GRC, Roberts was also recognized for the Best Oral Presentation at the fall 2010 meeting of the Genetics and Environmental Mutagenesis Society, winning a $1,500 travel award (see story(http://www.niehs.nih.gov/news/newsletter/2010/november/science-gems.cfm)).

Citation: Roberts SA,* Sterling J,* Yang Y,* Thompson C,* Malc E,# Mieczkowski P,# Resnick MA,* Gordenin DA.* 2011. Damage-Induced Localized Hypermutability at Double-Strand Breaks and Replication Forks.

* Chromosome Stability Group, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC27709

# Department of Genetics, Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, NC 27599-3280



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