A manuscript highlighting DNA double strand breaks that colocalized with chromosome translocation hotspots within the MLL and NUP98 genes, in collaboration with Dr. Andre Nussenzweig, was published in FY 2018, and a follow-up manuscript was published in FY2019. We have also developed an in vivo model in which mice with decreased expression of Mcm2 (Mcm2 hypomorph) develop leukemia, with recurrent copy number alterations (CNA), involving known or suspected cancer-related genes. Nucleotide sequence of the breakpoints, primarily interstitial deletions, revealed features of NHEJ at the deletion junctions, and further showed that the deletions were enriched for mononucleotide repeats, consistent with the possibility that replication fork pausing, caused by limiting amounts of Mcm2 protein, preferentially led to DNA double strand breaks at mononucleotide repeats. These experiments were done in collaboration with CCR colleagues Drs. Meltzer and Nussenzweig, and a manuscript describing these findings has been submitted.
| Qiu, Zhijun; Zhang, Zhenhua; Roschke, Anna et al. (2017) Generation of Gross Chromosomal Rearrangements by a Single Engineered DNA Double Strand Break. Sci Rep 7:43156 |
| Canela, Andres; Maman, Yaakov; Jung, Seolkyoung et al. (2017) Genome Organization Drives Chromosome Fragility. Cell 170:507-521.e18 |
| Onozawa, Masahiro; Aplan, Peter D (2016) Templated Sequence Insertion Polymorphisms in the Human Genome. Front Chem 4:43 |
| Onozawa, Masahiro; Goldberg, Liat; Aplan, Peter D (2015) Landscape of insertion polymorphisms in the human genome. Genome Biol Evol 7:960-8 |
| Onozawa, Masahiro; Zhang, Zhenhua; Kim, Yoo Jung et al. (2014) Repair of DNA double-strand breaks by templated nucleotide sequence insertions derived from distant regions of the genome. Proc Natl Acad Sci U S A 111:7729-34 |
| Onozawa, Masahiro; Aplan, Peter D (2012) Illegitimate V(D)J recombination involving nonantigen receptor loci in lymphoid malignancy. Genes Chromosomes Cancer 51:525-35 |
| Beachy, Sarah H; Aplan, Peter D (2010) Mouse models of myelodysplastic syndromes. Hematol Oncol Clin North Am 24:361-75 |
| Cheng, Yue; Zhang, Zhenhua; Keenan, Bridget et al. (2010) Efficient repair of DNA double-strand breaks in malignant cells with structural instability. Mutat Res 683:115-22 |
| Mrózek, Krzysztof; Harper, David P; Aplan, Peter D (2009) Cytogenetics and molecular genetics of acute lymphoblastic leukemia. Hematol Oncol Clin North Am 23:991-1010, v |
