Page 38 - 2014 Printable Abstract Book
P. 38
basis of cancer stem cell radiation resistance and potential strategies to predict therapeutic outcomes and
overcome radioresistance.
(S401) Polycomb group proteins and their histone modifications in response to IR-induced DNA damage.
Michael Hendzel; Hilmar Strickfaden; Mohammad Ali, PhD; Darin McDonald, M.Sc.; Stuart Campbell,
M.Sc.; and Ismail Ismail, PhD, University of Alberta, Edmonton, Canada
The Polycomb group proteins are a family of proteins that were first characterized in Drosophila
as regulators of differentiation and cellular memory. There are two main enzymatic complexes that
account for this function, Polycomb repressive complex 1 (PRC1) and Polycomb repressive complex 2
(PRC2). They are now well-established regulators of differentiation where they are involved in the
repression of tissue-specific genes and the maintenance of the undifferentiated phenotype. Some family
members, such as BMI1, which is a subunit of PRC1, have been found to be overexpressed in solid tumors
and have particularly high expression in what are commonly referred to as cancer stem cells. Recently,
we [1-3] and others (reviewed in [4]) have shown that several Polycomb group proteins are recruited to
sites of DNA damage and the loss of either PRC1 or PRC2 contributes to radiation sensitivity. This provides
an attractive explanation for the observed increased radiation and chemoresistance of isolated cancer
stem cell populations and knockdown of BMI1 has been shown to radiosensitize glioma stem cells [5]. I
will describe our results showing the mechanisms of recruitment of the PRC1 and PRC2 complexes, their
involvement with the posttranslational modification of histones near DNA double-strand breaks and I will
present data addressing the mechanisms whereby PRC1 and PRC2 contribute to the DNA damage
response. 1. Campbell S, Ismail IH, Young LC, Poirier GG, Hendzel MJ: Polycomb repressive complex 2
contributes to DNA double-strand break repair. Cell Cycle 2013, 12:2675-2683.
2. Ismail IH, Gagne JP, Caron MC, McDonald D, Xu Z, Masson JY, Poirier GG, Hendzel MJ: CBX4-mediated
SUMO modification regulates BMI1 recruitment at sites of DNA damage. Nucleic Acids Res 2012, 40:5497-
5510. 3. Ismail IH, Andrin C, McDonald D, Hendzel MJ: BMI1-mediated histone ubiquitylation promotes
DNA double-strand break repair. J Cell Biol 2010, 191:45-60. 4. Vissers JH, van Lohuizen M, Citterio E: The
emerging role of Polycomb repressors in the response to DNA damage. J Cell Sci 2012, 125:3939-3948. 5.
Facchino S, Abdouh M, Chatoo W, and Bernier G: BMI1 confers radioresistance to normal and cancerous
neural stem cells through recruitment of the DNA damage response machinery. J Neurosci 2010,
30:10096-10111.
(S402) Epigenetics of hematopoietic system response to irradiation. Igor Koturbash, Uni Arkansas
Medical Science, Little Rock, AR
Bone marrow is a target organ for ionizing radiation (IR). Exposure to IR results in a number of
pathological states, including hematological malignancies. The DNA damaging effects of irradiation in
bone marrow and their role in pathogenesis of hematological malignancies are known and relatively well
characterized. However, it has been recently shown that other effects, not associated with the direct
damage to DNA, can also be detected in the exposed bone marrow. Of particular interest are the effects
exerted by the exposure to IR on DNA methylation. The latter is the most studied mechanism of epigenetic
regulation that plays an important role during the development and maintenance of cellular homeostasis.
In bone marrow, DNA methylation is one of the major regulators of hematopoiesis. It is involved in cellular
36 | P a g e
overcome radioresistance.
(S401) Polycomb group proteins and their histone modifications in response to IR-induced DNA damage.
Michael Hendzel; Hilmar Strickfaden; Mohammad Ali, PhD; Darin McDonald, M.Sc.; Stuart Campbell,
M.Sc.; and Ismail Ismail, PhD, University of Alberta, Edmonton, Canada
The Polycomb group proteins are a family of proteins that were first characterized in Drosophila
as regulators of differentiation and cellular memory. There are two main enzymatic complexes that
account for this function, Polycomb repressive complex 1 (PRC1) and Polycomb repressive complex 2
(PRC2). They are now well-established regulators of differentiation where they are involved in the
repression of tissue-specific genes and the maintenance of the undifferentiated phenotype. Some family
members, such as BMI1, which is a subunit of PRC1, have been found to be overexpressed in solid tumors
and have particularly high expression in what are commonly referred to as cancer stem cells. Recently,
we [1-3] and others (reviewed in [4]) have shown that several Polycomb group proteins are recruited to
sites of DNA damage and the loss of either PRC1 or PRC2 contributes to radiation sensitivity. This provides
an attractive explanation for the observed increased radiation and chemoresistance of isolated cancer
stem cell populations and knockdown of BMI1 has been shown to radiosensitize glioma stem cells [5]. I
will describe our results showing the mechanisms of recruitment of the PRC1 and PRC2 complexes, their
involvement with the posttranslational modification of histones near DNA double-strand breaks and I will
present data addressing the mechanisms whereby PRC1 and PRC2 contribute to the DNA damage
response. 1. Campbell S, Ismail IH, Young LC, Poirier GG, Hendzel MJ: Polycomb repressive complex 2
contributes to DNA double-strand break repair. Cell Cycle 2013, 12:2675-2683.
2. Ismail IH, Gagne JP, Caron MC, McDonald D, Xu Z, Masson JY, Poirier GG, Hendzel MJ: CBX4-mediated
SUMO modification regulates BMI1 recruitment at sites of DNA damage. Nucleic Acids Res 2012, 40:5497-
5510. 3. Ismail IH, Andrin C, McDonald D, Hendzel MJ: BMI1-mediated histone ubiquitylation promotes
DNA double-strand break repair. J Cell Biol 2010, 191:45-60. 4. Vissers JH, van Lohuizen M, Citterio E: The
emerging role of Polycomb repressors in the response to DNA damage. J Cell Sci 2012, 125:3939-3948. 5.
Facchino S, Abdouh M, Chatoo W, and Bernier G: BMI1 confers radioresistance to normal and cancerous
neural stem cells through recruitment of the DNA damage response machinery. J Neurosci 2010,
30:10096-10111.
(S402) Epigenetics of hematopoietic system response to irradiation. Igor Koturbash, Uni Arkansas
Medical Science, Little Rock, AR
Bone marrow is a target organ for ionizing radiation (IR). Exposure to IR results in a number of
pathological states, including hematological malignancies. The DNA damaging effects of irradiation in
bone marrow and their role in pathogenesis of hematological malignancies are known and relatively well
characterized. However, it has been recently shown that other effects, not associated with the direct
damage to DNA, can also be detected in the exposed bone marrow. Of particular interest are the effects
exerted by the exposure to IR on DNA methylation. The latter is the most studied mechanism of epigenetic
regulation that plays an important role during the development and maintenance of cellular homeostasis.
In bone marrow, DNA methylation is one of the major regulators of hematopoiesis. It is involved in cellular
36 | P a g e
