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The ?eld of cellular responses to DNA damage has attained
widespread recognition and interest in recent years commensurate
with its fundamental role in the ma- tenance of genomic stability.
These responses, which are essential to preventing cellular death
or malignant transformation, are organized into a sophisticated s-
tem designated the "DNA damage response". This system operates in
all living organisms to maintain genomic stability in the face of
constant attacks on the DNA from a variety of endogenous
by-products of normal metabolism, as well as exogenous agents such
as radiation and toxic chemicals in the environment. The response
repairs DNA damage via an intricate cellular signal transduction
network that coordinates with various processes such as regulation
of DNA replication, tr- scriptional responses, and temporary cell
cycle arrest to allow the repair to take place. Defects in this
system result in severe genetic disorders involving tissue
degeneration, sensitivity to speci?c damaging agents,
immunode?ciency, genomic instability, cancer predisposition and
premature aging. The ?nding that many of the crucial players
involved in DNA damage response are structurally and functionally
conserved in different species spurred discoveries of new players
through similar analyses in yeast and mammals. We now understand
the chain of events that leads to instantaneous activation of the
massive cellular responses to DNA lesions. This book summarizes
several new concepts in this rapidly evolving ?eld, and the
advances in our understanding of the complex network of processes
that respond to DNA damage.
The ?eld of cellular responses to DNA damage has attained
widespread recognition and interest in recent years commensurate
with its fundamental role in the ma- tenance of genomic stability.
These responses, which are essential to preventing cellular death
or malignant transformation, are organized into a sophisticated s-
tem designated the "DNA damage response". This system operates in
all living organisms to maintain genomic stability in the face of
constant attacks on the DNA from a variety of endogenous
by-products of normal metabolism, as well as exogenous agents such
as radiation and toxic chemicals in the environment. The response
repairs DNA damage via an intricate cellular signal transduction
network that coordinates with various processes such as regulation
of DNA replication, tr- scriptional responses, and temporary cell
cycle arrest to allow the repair to take place. Defects in this
system result in severe genetic disorders involving tissue
degeneration, sensitivity to speci?c damaging agents,
immunode?ciency, genomic instability, cancer predisposition and
premature aging. The ?nding that many of the crucial players
involved in DNA damage response are structurally and functionally
conserved in different species spurred discoveries of new players
through similar analyses in yeast and mammals. We now understand
the chain of events that leads to instantaneous activation of the
massive cellular responses to DNA lesions. This book summarizes
several new concepts in this rapidly evolving ?eld, and the
advances in our understanding of the complex network of processes
that respond to DNA damage.
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