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Research in the Andreassen Laboratory at Cincinnati Children’s Hospital Medical Center focuses on the relationship of DNA repair and cell cycle checkpoints to the genetic instability that underlies the development of cancer. In particular, we are studying basic cellular mechanisms that respond to DNA damage, including breast cancer susceptibility (BRCA) and Fanconi anemia (FA) genes and proteins. Each of these genes prevents chromosome instability and promotes resistance to DNA interstrand crosslinking agents, such as mitomycin C (MMC). The FA / BRCA genes are associated with a predisposition to various cancers, and FA is also linked to aplastic anemia and congenital anomalies.
Duan W, Gao L, Zhao W, Leon M, Sadee W, Webb A, Resnick K, Wu X, Ramaswamy B, Cohn DE, Shapiro C, Andreassen PR, Otterson GA, Villalona-Calero MA. Assessment of FANCD2 nuclear foci formation in paraffin-embedded tumors: a potential patient-enrichment strategy for treatment with DNA interstrand crosslinking agents. Translational Research 161, 3:56-64.
Park JY, Singh TR, Nassar N, Zhang F, Freund M, Hanenberg H, Meetei AR, Andreassen PR. Breast cancer-associated missense mutants of the PALB2 WD40 domain, which directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair. Oncogene Epub Oct. 21.
Du W, Rani R, Sipple J, Schick J, Myers KC, Mehta P, Andreassen PR, Davies SM, Pang Q. The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters. Blood. 119, 18: 4142-4151.
Sin HS, Barski A, Zhang F, Kartashov AV, Nussenzweig A, Chen J, Andreassen PR, Namekawa SH. RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in post-meiotic spermatids. Genes & Development, 26, 24:2737-2748.
Zhang F, Bick G, Park JY, Andreassen PR. MDC1 and RNF8 function in a pathway that directs BRCA1-dependent localization of PALB2 required for homologous recombination. Journal of Cell Science, 125, 24:6049-6057.
Ichijima Y, Ichijima M, Lou Z, Nussenzweig A, Camerini-Otero RD, Chen J, Andreassen PR, Namekawa SH. MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells. Genes & Development. 25, 9: 959-971.
Kavanaugh G.M., Wise-Draper T.M., Morreale R.J., Morrison M.A., Gole B., Schwemberger S., Tichy E.D., Lu L., Babcock G.F., Wells J.M., Drissi R., Bissler J.J., Stambrook P.J., Andreassen P.R., Wiesmuller L., Wells S.I. The human DEK oncogene regulates DNA damage response signaling and repair. Nucleic Acids Research. 39, 17: 7465-7476.
Melendez J, Stengel K, Zhou X, Chauhan BK, Debidda M, Andreassen P, Lang RA, Zheng Y. RhoA GTPase is dispensable for actomyosin regulation but is essential for mitosis in primary mouse embryo fibroblasts. Journal of Biological Chemistry. 286, 17: 15132-15137.
Montes de Oca R., Andreassen P.R., Wilson K.L. Barrier-to-autointegration factor influences specific histone modifications. Nucleus. 2, 6: 580-590.
Hayakawa T, Zhang F, Hayakawa N, Ohtani Y, Shinmyozu K, Nakayama J, Andreassen PR. MRG15 binds directly to PALB2 and stimulates homology-directed repair of chromosomal breaks. Journal of Cell Science. 127, 7: 1124-1130. 2010.
Li, J., Du W., Maynard S., Andreassen P.R., Pang Q. Oxidative stress-specific interaction between FANCD2 and FOXO3a. Blood. 115, 8: 1545-1548.
Witt K.L., Moorman P.G., Kovalchuk O., Holland N., Block G., Andreassen P.R. Genetics and women’s health issues-the commitment of EMS to women scientists and gender-associated disease topics. Environmental and Molecular Mutagenesis. 51, 8-9: 774-780.
Zhang F., Fan Q., Ren K., Auerbach A.D., Andreassen PR. FANCJ/BRIP1 recruitment and regulation of FANCD2 in DNA damage responses. Chromosoma. 119, 6: 637-649.
Andreassen PR, Niedernhofer LJ. Fanconi anemia: a paradigm of discovering molecular pathways from patients. Mutation Research /Fundamental and Molecular Mechanisms of Mutagenesis. 668, 1-2: 1-3. 2009.
Andreassen PR, Ren K. Fanconi anemia proteins, DNA interstrand crosslink repair pathways, and cancer therapy. Current Cancer Drug Targets. 9, 1: 101-117. 2009.
Fan Q, Zhang F, Barrett B, Ren K, Andreassen PR. A role for monoubiquitinated FANCD2 at telomeres in ALT cells. Nucleic Acids Research. 37, 6: 1740-1754. 2009.
Pang Q, Andreassen PR. Fanconi anemia proteins and endogenous stresses. Mutation Research /Fundamental and Molecular Mechanisms of Mutagenesis. 668, 1-2: 42-53. 2009.
Singh TR, Bakker ST, Agarwal S, Jansen M, Grassman E, Godthelp BC, Ali AM, Du CH, Rooimans MA, Dan Q, Wahengbam K, Steltenpool J, Andreassen PR, Williams DA, Joenje H, de Winter JP, Meetei AR. Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood. 114, 1: 174-180. 2009.
Zhang F, Fan Q, Ren K, Andreassen PR. PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2. Molecular Cancer Research. 7, 7: 1110-1118. 2009.
Krejci O, Wunderlich M, Geiger H, Chou FS, Schleimer D, Jansen M, Andreassen PR, Mulloy JC. p53 signaling in response to increased DNA damage sensitizes AML1-ETO cells to stress-induced death. Blood. 111, 4: 2190-2199. 2008.
Singh TR, Ali AM, Busygina V, Raynard S, Fan Q, Du CH, Andreassen PR, Sung P, Meetei AR. BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome. Genes & Dev. 22, 20: 2856-2868. 2008.
Andreassen PR, Ho G, D’Andrea AD. DNA damage responses and their many interactions with the replication fork. Carcinogenesis. 25, 5: 883-892. 2006.
Cantor SB, Andreassen PR. Assessing the link between BACH1 and BRCA1 in the FA pathway. Cell Cycle. 5, 2: 164-167. 2006.
Litman R, Peng M, Jin Z, Zhang F, Zhang J, Powell S, Andreassen PR, Cantor SB. BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ. Cancer Cell. 8, 3: 255-265. 2005.
Andreassen PR, D’Andrea AD, Taniguchi T. ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes & Development. 18, 16: 1958-1963.2004.
Skoufias DA, Lacroix FB, Andreassen PR, Wilson L, Margolis RL. Inhibition of DNA decatenation, but not DNA damage, arrests cells at metaphase. Molecular Cell. 15, 6: 977-990. 2004.
Wang XZ, Andreassen PR, D’Andrea AD. Functional Interaction of FANCD2 and BRCA2 / FANCD1 in chromatin. Molecular and Cellular Biol. 24, 13:5850-5862. 2004.
Mollinari C, Reynaud C, Martineau-Thuillier S, Monier S, Kieffer S, Garin J, Andreassen PR, Boulet A, Goud B, Kleman JP, Margolis RL. The mammalian passenger protein TD-60 is an RCC1 family member with an essential role in prometaphase to metaphase progression. Developmental Cell. 5, 2: 295-307.2003.
Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Lane WS, Kim ST, Kastan MB, D’Andrea AD. Convergence of the Fanconi Anemia and Ataxia Telangiectasia signaling pathways. Cell. 109, 4: 459-472.2002.
Taniguchi T, Garcia-Higuera I, Andreassen PR, Gregory RC, Grompe M, D’Andrea AD. S-phase-specific interaction of the Fanconi Anemia protein, FANCD2, with BRCA1 and RAD51. Blood. 100, 7: 2414-2420. 2002.
Andreassen PR, Lacroix FB, Lohez OD, Margolis RL. Neither p21WAF1 nor 14-3-3sigma prevents G2 progression to mitotic catastrophe in human colon carcinoma cells after DNA damage, but p21WAF1 induces stable G1 arrest in resulting tetraploid cells. Cancer Research. 61, 20: 7660-7668.2001.
Andreassen PR, Lohez OD, Lacroix FB, Margolis RL. Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1.Molecular Biology of the Cell. 12, 5: 1315-1328.2001.
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For information regarding the Andreassen Lab contact:
Dr. Paul Andreassen513-636-0499Paul.Andreassen@cchmc.org
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