dc.description.abstract |
"The eukaryotic genome is systematically packaged into a topologically complex, fibrous
superstructure known as chromatin in order to accommodate within the nucleus of the
cell. The most basic repeating unit of chromatin is the nucleosome core particle (NCP)
that is essentially made up of 146 bp of DNA wrapped in roughly two super helical turns
around an octamer of core histones (Luger et al., 1997). The entire genomic DNA thus
packaged into repeating units of the nucleosome resembles a “beads on a string” structure
(Baer and Kornberg, 1979; Klug et al., 1980; Olins and Olins, 1979). Further higher order
packaging of NCPs into fibers is a multi-step phenomenon (Figure 1.1) and requires
several proteins such as linker histone H1 and histone tails which interacts with NCPs and
organizes the linker DNA. Many additional levels of folding involving linker histone H1
(Thomas and Stott, 2012), non-histone proteins such as HMGs, HP1, PC4 (Das et al.,
2010a; Das et al., 2006), MENT (Luger and Hansen, 2005), DEK (Kappes et al., 2011;
Waldmann et al., 2002), PARP-1 (Galande and Kohwi-Shigematsu, 2000), CTCF and
non-coding RNAs facilitate the accommodation of the vast expanse of eukaryotic genome
into the limited confines of the nucleus (Luger, 2006) (Figure 1.1). However, in spite of
such higher degree of compaction, the eukaryotic chromatin is highly dynamic in nature
with diversity being generated through local chromatin composition (presence of histone
variants) (Henikoff et al., 2004), covalent modifications of histones (Strahl and Allis,
2000), methylation status of the DNA, histone chaperones and the ATP dependent
chromatin remodeling which ensures the progress of various DNA-templated nuclear
processes such as replication, transcription and repair (Becker and Workman, 2013)." |
en_US |