Browsing by Subject "break-induced replication (BIR)"

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    Break-Induced Replication and Genome Stability
    (MDPI, 2012-10-16) Sakofsky, Cynthia J.; Ayyar, Sandeep; Malkova, Anna; Biology, School of Science
    Genetic instabilities, including mutations and chromosomal rearrangements, lead to cancer and other diseases in humans and play an important role in evolution. A frequent cause of genetic instabilities is double-strand DNA breaks (DSBs), which may arise from a wide range of exogeneous and endogeneous cellular factors. Although the repair of DSBs is required, some repair pathways are dangerous because they may destabilize the genome. One such pathway, break-induced replication (BIR), is the mechanism for repairing DSBs that possesses only one repairable end. This situation commonly arises as a result of eroded telomeres or collapsed replication forks. Although BIR plays a positive role in repairing DSBs, it can alternatively be a dangerous source of several types of genetic instabilities, including loss of heterozygosity, telomere maintenance in the absence of telomerase, and non-reciprocal translocations. Also, mutation rates in BIR are about 1000 times higher as compared to normal DNA replication. In addition, micro-homology-mediated BIR (MMBIR), which is a mechanism related to BIR, can generate copy-number variations (CNVs) as well as various complex chromosomal rearrangements. Overall, activation of BIR may contribute to genomic destabilization resulting in substantial biological consequences including those affecting human health.
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    STABILITY OF GAA/TTC AND CTG/CAG TRINUCLEOTIDE REPEATS DURING BREAK-INDUCED REPLICATION IN YEAST
    (Office of the Vice Chancellor for Research, 2012-04-13) Chen, Yu-Hsiang; Malkova, Anna
    Several human neurodegenerative disorders are caused by the expansion of trinucleotide repeats within or near the region of genes. To study the sta-bility of trinucleotide repeats in eukaryotic cells, we insert different number of GAA and CTG repeats in both orientations separately into the genome of Saccharomyces cerevisiae. In addition to S-phase replications, DNA can also be repaired by break-induced replication (BIR), an important process of DNA repair system that has been implicated in various chromosomal instabilities. In this study, we want to analyze the stability of trinucleotide repeats asso-ciated with BIR.