thesis
Regulation of Homologous Recombination between Divergent DNA Sequences by Mismatch Repair Proteins
- Publication date
- 28 January 2014
- Publisher
- __Abstract__
Genomes of living organisms, from unicellular bacteria to multicellular human, are
threatened by a plethora of DNA lesions. It is estimated that there are ~100,000 DNA
lesions inflicted in a single cell on a daily basis (Lindahl, 1993). Both endogenous and
exogenous agents induce the formation of these lesions in the genome. Internally, other
than replication errors that generate DNA mismatches, reactive oxygen species,
alkylating agents and spontaneous hydrolysis damage DNA. These structural
alterations include oxidation, methylation, deamination, depurination and depyrimidation
of DNA bases. External agents such as ultraviolet radiation, high-frequency radiations
like X-rays and γ-rays, natural and synthetic toxins, can all damage DNA by changing its
structure. These agents mediate the formation of intra- and interstrand crosslinks, of
bulky adducts as well as of single- and double-strand breaks (DSBs) in the DNA. To
ensure proper operation of DNA transactions, which are important for cellular survival, a
variety of DNA-repair pathways act on these DNA lesions to preserve the integrity of the
genome (Hoeijmakers 2001, 2009; Friedberg 2003; Garinis et al., 2008). These DNArepair
pathways include DNA mismatch repair (MMR; Jiricny 2013), base excision repair
(BER; Goosen and Moolenaar, 2008), nucleotide excision repair (NER; Goosen and
Moolenaar, 2008), non-homologous end joining (NHEJ; Shuman and Glickman, 2