Biology Reference
In-Depth Information
Overview for the Histone
Codes for DNA Repair
Elizabeth A. Williamson,
*
Justin W. Wray,
{
Pranshu
{
Bansal,
and Robert Hromas
*
*Department of Medicine, University of
Florida, Gainesville, Florida, USA
{
Department of Medicine, University of
New Mexico, Albuquerque, New Mexico,
USA
I. Histone Modifications of Homologous Recombination Repair . . . . . . . . . . . . . . . . . . . . .
208
II. Histone Modifications of NHEJ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
215
III. Histone Modifications of Nucleotide Excision Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
217
IV. Histone Modifications of Base Excision Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
219
V. DNA Mismatch Repair and Histone Modifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
220
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
222
DNA damage occurs continuously as a result of various factors—intracellu-
lar metabolism, replication, and exposure to genotoxic agents, such as ionizing
radiation and chemotherapy. If left unrepaired, this damage could result in
changes or mutations within the cell genomic material. There are a number of
different pathways that the cell can utilize to repair these DNA breaks. How-
ever, it is of utmost interest to know how the DNA damage is signaled to the
various DNA pathways. As DNA damage occurs within the chromatin, we
postulate that modifications of histones are important for signaling the position
of DNA damage, recruiting the DNA repair proteins to the site of damage, and
creating an open structure such that the repair proteins can access the site of
damage. We discuss the modifications that occur on the histones and the
manner in which they relate to the type of damage that has occurred as well
as the DNA repair pathways that are activated.
Cells are exposed to many agents that can cause DNA damage and in order
to maintain genomic stability, this damage must be repaired. The signaling
pathways are well described from ataxia telangiectasia mutated/ATM and Rad3
related (ATM/ATR) through Chk1 and Chk2, which signal the cell in which
damage has occurred and needs to be repaired, but the signals that occur at the
site of damage are only now becoming better understood. Histones are nuclear
proteins that package and organize DNA into nucleosomes. There are five
types of histones: H1, H2A, H2B, H3, and H4. Histone H1 is involved in the
