SMB Faculty Profiles

Steven Roberts

Steven Roberts

Associate Professor
Room: BLS 335
Office Phone: 509-335-4934
Room: BLS 340
Lab Phone: 509-335-1421



Research & Interests

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.

Select Publications
  • Khodaverdian VY, Hanscom T, Yu AM, Yu TL, Mak V, Brown AJ, Roberts SA, McVey M. (2017) Secondary-structure forming sequences drive SD-MMEJ repair of DNA double-strand breaks.  Nucleic Acids Res 45(22):12848-12861. doi: 10.1093/nar/gkx1056. PMID: 29121353 PMCID: PMC5728401
  • Mao P, Brown AJ, Malc EP, Mieczkowski PA, Smerdon MJ, Roberts SA, Wyrick JJ. (2017) Genome-wide Maps of Alkylation Damage, Repair, and Mutagenesis Reveal Mechanisms of Mutational Heterogeneity Genome Res 27(10):1674-1684. doi: 10.1101/gr.225771.117. Epub 2017 Sep 14. PMID: 28912372 PMCID: PMC5630031
  • Hoopes JI, Hughes AL, Hobson LA, Cortez LM, Brown AJ, Roberts SA. (2017) Avoidance of APOBEC3B-induced mutation by error-free lesion bypass Nucleic Acids Res 45(9):5243-5254. doi: 10.1093/nar/gkx169. PMID: 28334887 PMCID: PMC5605239
  • Saini N, Roberts SA, Sterling JF, Malc EP, Mieczkowski PA, Gordenin DA. (2017) APOBEC3B cytidine deaminase targets the non-transcribed strand of tRNA genes in yeast DNA Repair (Amst) 53:4-14. doi: 10.1016/j.dnarep.2017.03.003. Epub 2017 Mar 21. PMID: 28351647 PMCID: PMC5450012
  • Mao P, Smerdon MJ, Roberts SA, Wyrick JJ (2016) Chromosomal landscape of UV damage formation and repair at single-nucleotide resolution. Pro Natl Acad Sci USE. 113(32), 9057-62 PMID: 27457959 PMCID: PMC4987812
  • 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, Gordenin DA. (2016) The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts. PLoS Genet. 12(10):e1006385. doi: 10.1371/journal.pgen.1006385. eCollection 2016 Oct. PMID: 27788131 PMCID: PMC5082821
  • Wyatt DW, Feng W, Conlin MP, Yousefzadeh MJ, Roberts SA, Mieczkowski P, Wood RD, Gupta GP, Ramsden DA. (2016) Essential Roles for Polymerase θ-Mediated End Joining in the Repair of Chromosome Breaks. Mol Cell. 63(4):662-673. doi: 10.1016/j.molcel.2016.06.020. Epub 2016 Jul 21. PMID: 27453047 PMCID: PMC4992412
  • Hoopes JI, Cortez LM, Mertz TM, Malc EP, Mieczkowski PA, Roberts SA. (2016) APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication.  Cell Rep 14(6):1273-1282. doi: 10.1016/j.celrep.2016.01.021. Epub 2016 Jan 28. PMID: 26832400 PMCID: PMC4758883
  • Sakofsky CJ, Roberts SA, Malc E, Mieczkowski PA, Resnick MA, Gordenin DA, Malkova A. (2014) Break-induced replication is a source of mutation clusters underlying kataegis. Cell Rep. 7(5), 1640-8 PMID: 24882007 PMCID: PMC4274036
  • Strande NT, Carvajal-Garcia J, Hallett RA, Waters CA, Roberts SA, Strom C, Kuhlman B, Ramsden DA (2014) Requirements for 5'dRP/AP lyase activity in Ku. Nucleic Acids Res. 42(17), 11136-43 PMID: 25200085 PMCID: PMC4176175
  • The Cancer Genome Atlas Research Network (2014) The somatic genomic landscape of chromophobe renal cell carcinoma Cancer Cell. PMID: PMCID:
  • Cancer Genome Atlas Research Network. (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 507(7492), 315-22 PMID: 24476821 PMCID: PMC3962515
  • Roberts SA, Gordenin, Dmitry A (2014) Clustered Mutations in Human Cancer. eLS. John Wiley & Sons Ltd, Chichester. PMID: PMCID:
  • Roberts SA, Gordenin DA (2014) Clustered and genome-wide transient mutagenesis in human cancers: Hypermutation without permanent mutators or loss of fitness. Bioessays. PMID: 24615916 PMCID: PMC4145046
  • Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA, Fargo D, Stojanov P, Kiezun A, Kryukov GV, Carter SL, Saksena G, Harris S, Shah RR, Resnick MA, Getz G, Gordenin DA. (2013) An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet. 45(9), 970-6 PMID: 23852170 PMCID: PMC3789062
  • Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, Kiezun A, Hammerman PS, McKenna A, Drier Y, Zou L, Ramos AH, Pugh TJ, Stransky N, Helman E, Kim J, Sougnez C, Ambrogio L, Nickerson E, Shefler E, Cortés ML, Auclair D, Saksena G, Voet D, Noble M, DiCara D, Lin P, Lichtenstein L, Heiman DI, Fennell T, Imielinski M, Hernandez B, Hodis E, Baca S, Dulak AM, Lohr J, Landau DA, Wu CJ, Melendez-Zajgla J, Hidalgo-Miranda A, Koren A, McCarroll SA, Mora J, Lee RS, Crompton B, Onofrio R, Parkin M, Winckler W, Ardlie K, Gabriel SB, Roberts CW, Biegel JA, Stegmaier K, Bass AJ, Garraway LA, Meyerson M, Golub TR, Gordenin DA, Sunyaev S, Lander ES, Getz G (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 499(7457), 214-8 PMID: 23770567 PMCID: PMC3919509
  • Roberts SA, Sterling J, Thompson C, Harris S, Mav D, Shah R, Klimczak LJ, Kryukov GV, Malc E, Mieczkowski PA, Resnick MA, Gordenin DA (2012) Clustered Mutations in Yeast and in Human Cancers Can Arise from Damaged Long Single-Strand DNA Regions. Mol Cell. 46(4), 424-35 PMID: 22607975 PMCID: PMC3361558
  • Chan K, Sterling JF, Roberts SA, Bhagwat AS, Resnick MA, Gordenin DA (2012) Base damage within single-strand DNA underlies in vivo hypermutability induced by a ubiquitous environmental agent. PLoS Genet. 8(12) PMID: 23271983 PMCID: PMC3521656
  • Strande N, Roberts SA, Oh S, Hendrickson EA, Ramsden DA (2012) Specificity of the dRP/AP lyase of Ku promotes nonhomologous end joining (NHEJ) fidelity at damaged ends. J Biol Chem. 287(17), 13686-93 PMID: 22362780 PMCID: PMC3340204
  • Burch LH, Yang Y, Sterling JF, Roberts SA, Chao FG, Xu H, Zhang L, Walsh J, Resnick MA, Mieczkowski PA, Gordenin DA (2011) Damage-induced localized hypermutability. Cell Cycle. 10(7), 1073-85 PMID: 21406975 PMCID: PMC3100884
  • Roberts SA, Strande N, Burkhalter MD, Strom C, Havener JM, Hasty P, Ramsden DA (2010) Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends. Nature. 464(7292), 1214-7 PMID: 20383123 PMCID: PMC2859099
  • Roberts SA, Ramsden DA (2007) Loading of the nonhomologous end joining factor, Ku, on protein-occluded DNA ends. J Biol Chem. 282(14), 10605-13 PMID: 17289670 PMCID:

List of Publications

Washington State University