Dr. Aaron Goodarzi

 BSc Hons; University of Calgary,  Ph.D.; University of Calgary,  Fellowship; University of Sussex
Assistant Professor, Biochemistry & Molecular Biology/Oncology

Affiliations: Member- Southern Alberta Cancer Research Institute, Member-Genome Stability and Ageing Group

Research Interests:

The technological age has seen humans increasingly exposed to sources of DNA-damaging radiation. A double-edged sword, radiation has enabled great advances in energy production, medical diagnosis and cancer therapy while simultaneously increasing our risk of nuclear accident or attack. The most deleterious lesion caused by radiation is a break in both strands of our DNA, a DNA double-strand break. Unless accurately repaired by the molecular machinery of our cells, DNA double-strand breaks can lead to genome instability - a fundamental driver of cancer and accelerated ageing.

Human DNA is naturally packaged around small protein complexes made up of histones, subdividing our DNA into manageable units called ‘nucleosomes'. Collectively, this complex of DNA and protein is referred to as ‘chromatin'. Mammalian chromatin exists within a gradient of comparably relaxed and accessible euchromatin to highly condensed and inaccessible heterochromatin - a distribution underlying the hugely increased size and complexity of our genome relative to our distant evolutionary ancestors.

We now know that DNA double-strand breaks occurring within regions of densely packaged and complex chromatin (heterochromatin) are much more difficult to repair compared to breaks occurring in open chromatin, requiring substantially longer to resolve following radiation exposure. Numerous additional molecular events need to occur in flawless succession to achieve the repair of a heterochromatic DNA double strand break. Among these events is the manipulation of the local nucleosome arrangement around the DNA double-strand break by so-called ‘nucleosome remodeling' enzymes. My research endeavors to understand how processes involving nucleosome remodeling enzymes underlie DNA double-strand break repair in complex chromatin and, in doing so, improve our knowledge of cancer formation, human ageing and radiation protection

Personnel:

• Goodarzi AA, Kurka T, Jeggo PA. KAP-1 phosphorylation disperses heterochromatic CHD3/Mi-2α nucleosome remodeling is regulated by KAP-1 phosphorylation during the DNA double strand break response. Nat. Struct. Mol. Biol. 2011. In press.
• Goodarzi AA, Jeggo PA. Irradiation induced foci (IRIF) as a biomarker for radiosensitivity and radiation exposure. Mutation Research. Review. In press.
• Goodarzi AA, Löbrich M, Jeggo PA. The influence of heterochromatin on DNA double strand break (DSB) repair: Getting the strong, silent type to relax. DNA Repair 2010. Review. In press.
• Woodbine L, Grigoriadou S, Goodarzi AA, Riballo E, Tape C, Oliver A, van Zelm, MC, Buckland MS, Davies EG, Pearl LH, Jeggo PA. An Artemis polymorphic variant reduces Artemis activity and confers cellular radiosensitivity. DNA Repair 2010. 9(9):1003-10.
• Shibata A, Barton O, Noon AT, Dahm K, Deckbar D, Goodarzi AA, Löbrich M, Jeggo PA. The role of ATM and the damage response mediator proteins, 53BP1 and MDC1, in the maintenance of G2/M checkpoint arrest. Mol. Cell. Biol. 2010. 30(13):3371-83.
• Noon AT, Shibata A, Rief N, Löbrich M, Stewart GS, Jeggo PA, Goodarzi AA. 53BP1 facilitates heterochromatic DNA double strand break repair by enabling highly localized KAP-1 phosphorylation. Nat. Cell Biol. 2010 Feb;12(2):177-84.
• Löbrich M, Shibata A, Beucher A, Fisher A, Ensminger M, Goodarzi AA, Barton O, Jeggo PA. γH2AX foci analysis for monitoring DNA double-strand break repair: Strengths, limitations and optimization Cell Cycle 2010. Feb 15;9:4, 1-8; Review.
• Lee J-H, Goodarzi AA, Jeggo PA, Paull T. 53BP1 promotes ATM activity through direct interactions with the MRN complex. EMBO J. 2010 Feb 3;29(3):574-85.
• Beucher A, Birraux J, Tchouandong L, Barton O, Shibata A, Rief N, Goodarzi AA, Krempler A, Jeggo PA and Löbrich M. A role for ATM and Artemis in homologous recombination repair of radiation-induced DNA double strand breaks. EMBO J. 2009 Nov 4;28(21):3413-27.
• Goodarzi AA, Noon AT, Jeggo PA. The impact of KAP-1 dependent heterochromatin on DSB repair. Biochem Soc Trans. 2009 Jun;37(Pt 3):569-76. Review.
• Goodarzi AA, Jeggo PA. "A mover and a shaker": 53BP1 allows DNA double strand breaks a chance to dance and unite. F1000 Biology Reports 2009, 1:21.  Review.
• Goodarzi AA, Noon AT, Jeggo PA. Heterochromatic DNA Double Strand Break Repair. Acta med. Nagasaki. 2009; 53: 13-17. Review.
• Shibata, A, Barton, O, Noon, AT, Dahm, K, Deckbar, D, Goodarzi, AA, Löbrich, M , Jeggo, PA. The maintenance of ATM dependent G2/M checkpoint arrest following exposure to ionizing radiation. Acta med. Nagasaki. 2009; 53: 19-21. Review.
• Riballo E, Woodbine L, Stiff T, Walker SA, Goodarzi AA, Jeggo PA. XLF-Cernunnos promotes DNA Ligase IV-XRCC4 readenylation following ligation. Nucl. Acid Res. 2009; 37(2):482-92.
• Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Löbrich M, Jeggo PA. ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell. 2008 31(2):167-77. (Evaluated & cited by F1000: www.f1000biology.com/article/1119144/evaluation) Commented in: Fernandez-Capetillo O, Nussenzweig A. ATM breaks into heterochromatin. Mol Cell. 2008 Aug 8;31(3):303-4.

Contact Information:
The University of Calgary
Room 306- Heritage Medical Research Building
3330 Hospital Drive NW
Calgary, Alberta Canada T2N 4N1
Phone (403) 220-4896
E-mail: a [dot] goodarzi [at] ucalgary [dot] ca