Break-Induced Replication and Genome Stability

Biomolecules

Cynthia J. Sakofsky¹  Sandeep Ayyar¹ 

[1] Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, USA;

关键词: double-strand break (DSB);    DNA repair;    break-induced replication (BIR);    recombination;   

DOI  :  10.3390/biom2040483

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.