Page 23 - 2014 Printable Abstract Book
P. 23
resolution to be utilized to guide therapy for patients after being entered into the health care system.
Recent developments indicate that EPR dosimetry based on both radiation induced changes in teeth and
nd
st
in nails now appears to be suitable for 1 and 2 stage triage.
TR15. CHROMATIN STRUCTURE AND RADIATION SENSITIVITY
(TR1501) Chromatin structure and radiation sensitivity. Tej Pandita, UT Southwestern Medical Center,
Dallas, MO
The chromatin complex, a dynamic DNA and protein structure, is known to change as required for
ongoing DNA metabolism including transcription, replication and DNA damage repair. During DNA
damage sensing and repair processes, chromatin structure needs to undergo several changes in order to
facilitate access by the repair machinery. Recent studies have enhanced the understanding of how
chromatin structure impact DNA repair mechanisms specifically in the selection of the appropriate DNA
double strand break (DSB) repair pathway. This choice is facilitated by chromatin modifying factors acting
through post-translational protein modification that enhance DNA detachment from histones and other
bound proteins blocking access to DNA damage sites. Post-translational covalent modifications of histones
have, therefore, emerged as key regulatory events in the DNA damage response (DDR).
Histones are the major protein components of chromatin and are subject to many types of
posttranslational modifications, especially on their flexible N-terminal tails. Based on the presence of
specific interactions between histone modifications and proteins involved in cellular metabolism, these
modifications may constitute a ‘‘histone code’’ that manages the epigenetic information regulating the
DDR especially DSB repair pathway choice. The pre-existing, or pre-damage, histone modifications may
be a critical determinant of the subsequent damage identification signal and as such would have
implications for the recruitment of repairosome factors specific to particular pathways. The role of
preexisting histone modifications and their impact on sensing of ionizing radiation induced DNA damage,
therefore, will form the first part of this presentation. Hierarchical signaling network that orchestrate
chromatin structural changes also facilitate the DNA DSB repair response. These networks coordinate cell-
cycle checkpoints involving multiple enzymatic activities to repair broken DNA ends. In the second part of
this presentation, we will discuss the role of DSB induced ATM-dependent MOF (a histone H4 acetyl-
transferase) phosphorylation (p-T392-MOF) and the significance of p-T392-MOF in DNA DSB pathway
choice. As with other areas of basic research, a detailed mechanistic understanding of chromatin
modifications that regulate gene expression and the DDR should advance development of effective
patient specific radiotherapies based on their own tumor epigenetic phenotype.
TR16. REVIEW ON RADIATION AND EXOSOMES
(TR1601) Review on Radiation and Exosomes. Munira A. Kadhim, Department of Biological and Medical
Sciences, Oxford Brookes University, Oxford, United Kingdom
Exosomes are 30-150 nm intraluminal cell-derived vesicles / microvesicles that are present in
many and perhaps all biological fluids, including blood, urine, and medium of cell cultures. They are loaded
with unique RNA and protein cargo and have a wide range of normal physiological functions such as their
role in mediating communication between cells. It is also becoming increasingly clear that exosomes have
21 | P a g e
Recent developments indicate that EPR dosimetry based on both radiation induced changes in teeth and
nd
st
in nails now appears to be suitable for 1 and 2 stage triage.
TR15. CHROMATIN STRUCTURE AND RADIATION SENSITIVITY
(TR1501) Chromatin structure and radiation sensitivity. Tej Pandita, UT Southwestern Medical Center,
Dallas, MO
The chromatin complex, a dynamic DNA and protein structure, is known to change as required for
ongoing DNA metabolism including transcription, replication and DNA damage repair. During DNA
damage sensing and repair processes, chromatin structure needs to undergo several changes in order to
facilitate access by the repair machinery. Recent studies have enhanced the understanding of how
chromatin structure impact DNA repair mechanisms specifically in the selection of the appropriate DNA
double strand break (DSB) repair pathway. This choice is facilitated by chromatin modifying factors acting
through post-translational protein modification that enhance DNA detachment from histones and other
bound proteins blocking access to DNA damage sites. Post-translational covalent modifications of histones
have, therefore, emerged as key regulatory events in the DNA damage response (DDR).
Histones are the major protein components of chromatin and are subject to many types of
posttranslational modifications, especially on their flexible N-terminal tails. Based on the presence of
specific interactions between histone modifications and proteins involved in cellular metabolism, these
modifications may constitute a ‘‘histone code’’ that manages the epigenetic information regulating the
DDR especially DSB repair pathway choice. The pre-existing, or pre-damage, histone modifications may
be a critical determinant of the subsequent damage identification signal and as such would have
implications for the recruitment of repairosome factors specific to particular pathways. The role of
preexisting histone modifications and their impact on sensing of ionizing radiation induced DNA damage,
therefore, will form the first part of this presentation. Hierarchical signaling network that orchestrate
chromatin structural changes also facilitate the DNA DSB repair response. These networks coordinate cell-
cycle checkpoints involving multiple enzymatic activities to repair broken DNA ends. In the second part of
this presentation, we will discuss the role of DSB induced ATM-dependent MOF (a histone H4 acetyl-
transferase) phosphorylation (p-T392-MOF) and the significance of p-T392-MOF in DNA DSB pathway
choice. As with other areas of basic research, a detailed mechanistic understanding of chromatin
modifications that regulate gene expression and the DDR should advance development of effective
patient specific radiotherapies based on their own tumor epigenetic phenotype.
TR16. REVIEW ON RADIATION AND EXOSOMES
(TR1601) Review on Radiation and Exosomes. Munira A. Kadhim, Department of Biological and Medical
Sciences, Oxford Brookes University, Oxford, United Kingdom
Exosomes are 30-150 nm intraluminal cell-derived vesicles / microvesicles that are present in
many and perhaps all biological fluids, including blood, urine, and medium of cell cultures. They are loaded
with unique RNA and protein cargo and have a wide range of normal physiological functions such as their
role in mediating communication between cells. It is also becoming increasingly clear that exosomes have
21 | P a g e
