Biomedical Engineering Reference
In-Depth Information
6
DNA Damage Response Research,
Inherent and Future Nano-Based
Interfaces
for Personalized Medicine
Madhu Dyavaiah, Lauren Endres, Yiching Hsieh,
William Towns, and Thomas J. Begley
CONTENTS
6.1. Introduction.to.DNA.Damage.Response........................................................................ 127
6.1.1
.
Nano-Features.Associated.with.Biological.Sensing.of.DNA.
Damage.and.the.Initial.Response........................................................................ 128
6.1.2. Nano-Features.of.Signals.from.DNA.Damage................................................... 130
6.1.3. Other.Responses.to.Strand.Breaks....................................................................... 131
6.2. Nano-Features.of.Strand.Break.Repair........................................................................... 132
6.2.1. Nano-Features.of.the.MRN.Complex.Used.in.Strand.Break.Repair.............. 132
6.2.2. MRN:.A.Controllable.Nanomachine................................................................... 134
6.3. Making.DNA.Building.Blocks.Post-DNA.Damage....................................................... 134
6.3.1. Regulation.of.RNR.Activity.................................................................................. 134
6.4. The.Future.for.Nanotechnology.in.DNA.Damage.Response.
and.Personalized.Medicine............................................................................................... 135
6.4.1. Sensing.Damaging.Agents.with.Nanotechnology............................................ 135
6.4.2. Nanotechnology-Based.Sequencing.of.DDR.Response.Genes:.
Entering.the.Era.of.Personalized.Medicine........................................................ 136
6.5. Conclusions.and.Perspectives.......................................................................................... 137
References..................................................................................................................................... 138
6.1 Introduction to DNA Damage Response
The.cellular.genome.is.under.continuous.assault.from.intracellular.and.external.sources,.
such.as.endogenous.free.radicals,.replication.errors,.and.environmental.agents.that.include.
ionizing. radiation. and. genotoxic. chemicals.. Such. assaults. lead. to. DNA. base. and. sugar.
modiications. as. well. as. single-stranded. or. double-stranded. DNA. breaks.. These. small.
changes.to.the.DNA.double.helix.can.lead.to.larger.problems..To.put.small.in.context,.it.is.
important.to.remember.that.the.diameter.of.the.DNA.double.helix.is.∼2.4.nm,.thus.giving.
cellular. genetic. material. at. least. two. feature. sizes. in. the. nano-range. and. justifying. its.
classiication.as.a.nanomaterial.(Mandelkern.et.al..1981)..In.fact,.each.10.base.pair.piece.of.
DNA.has.a.length.of.∼3.4.nm,.which.supports.the.notion.that.DNA.fragments.less.than.290.
base.pairs.have.all.x-,.y-,.and.z-dimensions.smaller.than.100.nm.
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