Chromatin Dynamics During Repair
The eukaryotic genome is organized as chromatin. Chromatin consists of the entire genomic DNA content wound around "basic" histone octomers, which are then organized into higher order structures in a cell cycle-dependent manner.
In general terms, there are three levels of chromatin organization:
In general terms, there are three levels of chromatin organization:
- DNA wraps around histone proteins forming nucleosomes; the "beads on a string" structure (euchromatin - permissive to transcription)
- Multiple histones wrap into a 30 nm fibre consisting of nucleosome arrays in their most compact form (heterochromatin - inhibitory to transcription)
- Higher-level DNA packaging of the 30 nm fibre into the metaphase chromosome (during mitosis and meiosis).
Dynamic Chromatin Organization
Epigenetic chemical modification of the structural proteins in chromatin alter the local chromatin structure. Histone proteins are modified by various post-translational modification to alter DNA packing. Acetylation of the histone C-terminal tail loosens chromatin to create a "relaxed" structure referred to as "euchromatin" which is permissive to replication and transcription. When certain residues of histones are methylated, they hold DNA together strongly and restrict access to various enzymes.
The basic repeat element of chromatin is the nucleosome, interconnected by sections of linker DNA. In addition to the core histones, there is the linker histone, H1, which contacts the exit/entry of the DNA strand on the nucleosome. The nucleosome core particle, together with histone H1, is known as a chromatosome.
Nucleosomes, with about 20 to 60 base pairs of linker DNA, can form, under non-physiological conditions, an approximately 10 nm "beads-on-a-string" fibre. (Fig. 1-2).
The nucleosomes bind DNA non-specifically, as required by their function in general DNA packaging. There are, however, large DNA sequence preferences that govern nucleosome positioning. This is due primarily to the varying physical properties of different DNA sequences: For instance, adenosine and thymine are more favorably compressed into the inner minor grooves. This means nucleosomes can bind preferentially at one position approximately every 10 base pairs (the helical repeat of DNA)- where the DNA is rotated to maximise the number of A and T bases that will lie in the inner minor groove. (See mechanical properties of DNA.)
Epigenetic chemical modification of the structural proteins in chromatin alter the local chromatin structure. Histone proteins are modified by various post-translational modification to alter DNA packing. Acetylation of the histone C-terminal tail loosens chromatin to create a "relaxed" structure referred to as "euchromatin" which is permissive to replication and transcription. When certain residues of histones are methylated, they hold DNA together strongly and restrict access to various enzymes.
The basic repeat element of chromatin is the nucleosome, interconnected by sections of linker DNA. In addition to the core histones, there is the linker histone, H1, which contacts the exit/entry of the DNA strand on the nucleosome. The nucleosome core particle, together with histone H1, is known as a chromatosome.
Nucleosomes, with about 20 to 60 base pairs of linker DNA, can form, under non-physiological conditions, an approximately 10 nm "beads-on-a-string" fibre. (Fig. 1-2).
The nucleosomes bind DNA non-specifically, as required by their function in general DNA packaging. There are, however, large DNA sequence preferences that govern nucleosome positioning. This is due primarily to the varying physical properties of different DNA sequences: For instance, adenosine and thymine are more favorably compressed into the inner minor grooves. This means nucleosomes can bind preferentially at one position approximately every 10 base pairs (the helical repeat of DNA)- where the DNA is rotated to maximise the number of A and T bases that will lie in the inner minor groove. (See mechanical properties of DNA.)