Genomic stability is maintained by telomeres, the end terminal structures that protect chromosomes from fusion or degradation. Shortening or loss of telomeric repeats or altered telomere
chromatin structure is correlated with telomere dysfunction such as chromosome end-to-end associations that could lead to
genomic instability and gene amplification. The structure at the end of telomeres is such that its
DNA differs from
DNA double strand breaks (DSBs) to avoid nonhomologous end-joining (NHEJ), which is accomplished by forming a unique higher order
nucleoprotein structure. Telomeres are attached to the nuclear matrix and have a unique
chromatin structure. Whether this special structure is maintained by specific
chromatin changes is yet to be thoroughly investigated.
Chromatin modifications implicated in transcriptional regulation are thought to be the result of a code on the
histone proteins (histone code). This code, involving phosphorylation, acetylation, methylation, ubiquitylation, and sumoylation of
histones, is believed to regulate
chromatin accessibility either by disrupting
chromatin contacts or by recruiting non-
histone proteins to
chromatin. The histone code in which distinct
histone tail-
protein interactions promote engagement may be the deciding factor for choosing specific
DSB repair pathways. Recent evidence suggests that such mechanisms are involved in DNA damage detection and repair. Altered telomere
chromatin structure has been linked to defective DNA damage response (DDR), and eukaryotic cells have evolved DDR mechanisms utilizing proficient DNA repair and cell cycle checkpoints in order to maintain
genomic stability. Recent studies suggest that
chromatin modifying factors play a critical role in the maintenance of
genomic stability. This review will summarize the role of DNA damage repair
proteins specifically
ataxia-telangiectasia mutated (ATM) and its effectors and the telomere complex in maintaining
genome stability.