Participating Faculty

Steven-Roberts-lg

Steven Roberts

Department:School of Molecular Biosciences
Credentials:2008 - Ph.D., University of North Carolina - Biochemistry
Office:Biotechnology/Life Sciences 335
Phone:509-335-4934
Mailing Address:PO Box 647520
Pullman, WA 99164-7520
Email:steven.roberts2@wsu.edu
Website:Click here


Research Interests

Genetic alterations-mutations and chromosomal rearrangements

Research Summary

Mutations and chromosomal rearrangements underlie a variety of diseases from autism to cancer. What causes these genetic alterations, however, is frequently unclear. Recent large scale re-sequencing of human tumor genomes has revealed that cancer is a complex set of diseases, with tumors displaying different clinical and cellular characteristics. Along with these phenotypic differences, tumors have varying mutation frequencies and mutagenic processes occurring that ultimately impact aspects of disease onset, progression, and ultimately drug resistance. The focus of my lab is to understand the plasticity of genomes and how such alteration contributes to each of these aspects of carcinogenesis. We use biochemical, genetic, and genomic approaches to probe these questions.

One specific aspect of my research concerns the mutagenic nature of lesions in single-stranded (ss) DNA. Lesions that occur in single-stranded DNA are difficult to remove by traditional DNA excision repair pathways since these processes require the use of the complementary DNA strand. Using yeast as a model organism, my research has determined that ssDNA intermediates formed during normal DNA transactions like DNA double strand break repair and DNA replication are prone to base damage. Failure to accurately remove these lesions can lead to the formation of "mutation clusters." Lesions in ssDNA are also a frequent cause of mutations in human cancers. By analyzing mutations occurring across the genome of re-sequenced tumors, I have found that the APOBEC family of cytidine deaminases deaminate cytidine in ssDNA leading to increased mutation frequencies in specific tumor types. My research addresses how lesions in ssDNA are processed, what types of genetic alterations they induce, and how endogenous APOBEC activity is unleashed during cancer progression. Ultimately we are interested in how these processes contribute to cancer and whether they can be prevented to mitigate disease.

Research Publications

Khodaverdian V, Hanscom T, Yu A, Yu T, Mak V, Brown AJ, Roberts SA, and McVey M (2017) Secondary-structure forming sequences drive SD-MMEJ repair of DNA double-strand breaks. Nucleic Acids Research. Published Nov. 7. https://doi.org/10.1093/nar/gkx1056

Mao P, Brown AJ, Malc EP, Mieczkowski PA, Smerdon MJ, Roberts SA*, and Wyrick JJ (2017) Genome-wide Maps of Alkylation Damage, Repair, and Mutagenesis Reveal Mechanisms of Mutational Heterogeneity. Genome Research. 27: 1674-1684; Published in Advance September 14, 2017, doi:10.1101/gr.225771.117. PMID: 28912372 PMCID: PMC5630031  *Co-corresponding author

Hoopes JI, Hughes AL, Hobson LA, Cortez LM, Brown AJ, and Roberts SA* (2017) Avoidance of APOBEC3B-induced mutation by error-free lesion bypass. Nucleic Acids Research. 45(9):5243-5254. doi: 10.1093/nar/gkx169. PubMed PMID: 28334887. *Corresponding author.

Saini A, Roberts SA, Sterling JF, Malc EP, Mieczkowski PA, and Gordenin DA (2017) APOBEC3B cytidine deaminase targets the non-transcribed strand of tRNA genes in yeast. DNA Repair. 53:4-14. doi: 10.1016/j.dnarep.2017.03.003. Epub 2017 Mar 21. PubMed PMID: 28351647.

The Cancer Genome Atlas Research Network (2017) Integrated molecular characterization of invasive cervical cancer. Nature. 543:378-384. doi:10.1038/nature21386.

Saini N, Roberts SA, Klimczak LJ, Chan K, Grimm SA, Dai S, Fargo DC, Boyer JC, Kaufmann WK, Taylor JA, Lee E, Cortes-Ciriano I, Park PJ, Schurman SH, Malc EP, Mieczkowski PA, and Gordenin DA (2016) The impact of environmental and endogenous damage on human somatic mutation load. PLoS Genetics. 12(10):e1006385. doi: 10.1371/journal.pgen.1006385. PMID:27788131

Mao P, Smerdon MJ, Roberts SA, and Wyrick JJ (2016) Chromosomal Landscape of UV Damage Formation and Repair at Single Nucleotide Resolution. PNAS. 113(32):9057-62. doi: 10.1073/pnas.1606667113. Epub 2016 Jul 25.

Wyatt DW, Feng W, Conlin MP, Yousefzadeh MJ, Roberts SA, Mieczkowski P, Wood RD, Gupta GP, and Ramsden DA (2016) Essential roles for Polymerase  mediated end-joining in repair of chromosome breaks. Molecular Cell. 63(4):662-673. doi:http://dx.doi.org/10.1016/j.molcel.2016.06.020.

Hoopes JI, Cortez LM, Mertz TM, Malc EP, Mieczkowski PA, and Roberts SA* (2016) APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication. Cell Reports. 14(6):1273-82. PMID:26832400. *Corresponding author.

 

Washington State University