Abstract
Cells are constantly exposed to a variety of environmental and endogenous conditions causing DNA damage, which is detected and repaired by conserved DNA repair pathways to maintain genomic integrity. Chromatin remodeling is critical in this process, as the organization of eukaryotic DNA into compact chromatin presents a natural barrier to all DNA-related events. Studies on human premature aging syndromes together with normal aging have suggested that accumulated damages might lead to exhaustion of resources that are required for physiological functions and thus accelerate aging. In this manuscript, combining the present understandings and latest findings, we focus mainly on discussing the role of chromatin remodeling in the repair of DNA double-strand breaks (DSBs) and regulation of aging.
Highlights
The fundamental units of chromatin are the nucleosome core particles consisting of 147 base pairs of DNA wrapped around a histone octamer which is comprised of a central (H3-H4)2 tetramer flanked by two H2A-H2B dimers, in 1.65 left-handed helical turns [1,2,3]
It is becoming clear that chromatin conformation changes mediated by covalent histone modifications and ATP-dependent chromatin remodelers are essential for the efficient repair of double-strand breaks (DSBs), which is highly conserved across species
The chromatin remodeling and DSB repair pathways are critical for physiological V(D)J recombination, class switch recombination (CSR), meiosis etc
Summary
The fundamental units of chromatin are the nucleosome core particles consisting of 147 base pairs (bp) of DNA wrapped around a histone octamer which is comprised of a central (H3-H4) tetramer flanked by two H2A-H2B dimers, in 1.65 left-handed helical turns [1,2,3]. By histone deposition onto DNA, strings of 10nm nucleosome arrays are formed. Further packing and condensation of these nucleosome arrays through histone chaperones and chromatin remodelers initiate the hierarchy of chromatin assembly from 30 nm chromatin fiber to chromatin and culminate in chromosomes. Besides the canonical histone proteins (those that constitute nucleosomes), there exist histone variants which are isoforms of histone molecules, and they are deposited onto DNA in a sequence, and chromosomal region, specific manner to fulfill their distinct functions [4, 5]. H2A variants are the most investigated histone variants due to their pivotal roles in mediating DNA damage response and in regulating chromosome stability [6,7,8]
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