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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.
Konstantinidis DG, Giger KM, Risinger M, Pushkaran S, Zhou P, Dexheimer P, Yerneni S, Andreassen P, Klingmüller U, Palis J, Zheng Y, Kalfa TA. Cytokinesis failure in RhoA-deficient mouse erythroblasts involves actomyosin and midbody dysregulation and triggers p53 activation. Blood. 2015 Jul 30. [Epub ahead of print]
Kato Y, Alavattam KG, Sin HS, Meetei AR, Pang Q, Andreassen PR, Namekawa SH. FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis. Hum Mol Genet. 2015 Jun 29. [Epub ahead of print]
Zhang T, Wilson AF, Mahmood Ali A, Namekawa SH, Andreassen PR, Ruhikanta Meetei A, Pang Q. Loss of Faap20 Causes Hematopoietic Stem and Progenitor Cell Depletion in Mice Under Genotoxic Stress. Stem Cells. 2015 Jul;33(7):2320-30.
Hasegawa K, Sin HS, Maezawa S, Broering TJ, Kartashov AV, Alavattam KG, Ichijima Y, Zhang F, Bacon WC, Greis KD, Andreassen PR, Barski A, Namekawa SH. SCML2 establishes the male germline epigenome through regulation of histone H2A ubiquitination. Dev Cell. 2015 Mar 9;32(5):574-88.
Lombardi AJ, Hoskins EE, Foglesong GD, Wikenheiser-Brokamp KA, Wiesmüller L, Hanenberg H, Andreassen PR, Jacobs AJ, Olson SB, Keeble WW, Hays LE, Wells SI. Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers. Clin Cancer Res. 2015 Apr 15;21(8):1962-72.
Park JY, Zhang F, Andreassen PR. PALB2: the hub of a network of tumor suppressors involved in DNA damage responses. Biochim Biophys Acta. 2014 Aug;1846(1):263-75.
Broering TJ, Alavattam KG, Sadreyev RI, Ichijima Y, Kato Y, Hasegawa K, Camerini-Otero RD, Lee JT, Andreassen PR, Namekawa SH. BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis. J Cell Biol. 2014 Jun 9;205(5):663-75.
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. 2014 Oct 2;33(40):4803-12.
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. 2012 May 3;119(18):4142-51.
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 Dev. 2012 Dec 15;26(24):2737-48.
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. J Cell Sci. 2012 Dec 15;125(Pt 24):6049-57.
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 Dev. 2011 May 1;25(9):959-71.
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. J Cell Sci. 2010 Apr 1;123(Pt 7):1124-30.
Zhang F, Fan Q, Ren K, Andreassen PR. PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2. Mol Cancer Res. 2009 Jul;7(7):1110-8.
Fan Q, Zhang F, Barrett B, Ren K, Andreassen PR. A role for monoubiquitinated FANCD2 at telomeres in ALT cells. Nucleic Acids Res. 2009 Apr;37(6):1740-54.
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. 2005 Sep;8(3):255-65.
Andreassen PR, D'Andrea AD, Taniguchi T. ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes Dev. 2004 Aug 15;18(16):1958-63.
Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim ST, Lane WS, Kastan MB, D'Andrea AD. Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Cell. 2002 May 17;109(4):459-72.
Andreassen PR, Lohez OD, Lacroix FB, Margolis RL. Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. Mol Biol Cell. 2001 May;12(5):1315-28.
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 Res. 2001 Oct 15;61(20):7660-8.
Andreassen PR, Margolis RL. Microtubule dependency of p34cdc2 inactivation and mitotic exit in mammalian cells. J Cell Biol. 1994 Nov;127(3):789-802.
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For information regarding the Andreassen Lab contact:
Dr. Paul Andreassen513-636-0499Paul.Andreassen@cchmc.org
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