ABSTRACT The DNA damage response (DDR) is the signaling cascade that recognizes double-strand breaks (DSBs) and promotes their resolution via repair pathways of non-homologous end joining (NHEJ) or homologous recombination (HR). We others have shown DDR activation requires DROSHA; however, whether DROSHA exerts its functions by associating with sites, what controls recruitment, how influences r...

DNA double-strand breaks (DSBs) are repaired by either homologous recombination (HR) or non-homologous end joining (NHEJ) in mammalian cells. Repair with NHEJ or HR using single-strand annealing (SSA) often results in deletions and is generally referred to as non-conservative recombination. Error-free, conservative HR involves strand invasion and requires a homologous DNA template, and therefor...

Inactivation of the DNA mismatch repair pathway manifests as microsatellite instability, an accumulation of mutations that drives carcinogenesis. Here, we determined whether microsatellite instability in acute myeloid leukemia and myelodysplastic syndrome correlated with chromosomal instability and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity through disruption of DNA repair functi...

Alterations in the homologous repair pathway are thought to occur in 30%-50% of epithelial ovarian cancers. Cells deficient in homologous recombination rely on alternative pathways for DNA repair in order to survive, thereby providing a potential target for therapy. Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, capitalizes on this concept and is the first drug in its class approved ...

Preserving the integrity of the DNA double helix is crucial for the maintenance of genomic stability. Therefore, DNA double-strand breaks represent a serious threat to cells. In this review, we describe the two major strategies used to repair double strand breaks: non-homologous end joining and homologous recombination, emphasizing the mutagenic aspects of each. We focus on emerging evidence th...

We demonstrated repair of a double-stranded DNA gap through gene conversion by a homologous DNA sequence in Escherichia coli. We made a double-stranded gap in one of the two regions of homology in an inverted orientation on a plasmid DNA molecule and introduced it into an E. coli strain which has the RecE system of recombination (genotype; sbcA23 recB21 recC22). We detected repair products by g...

Significance Replication stress can affect development and is a hallmark of cancers. Warsaw breakage syndrome developmental disorder caused by mutations in the conserved DDX11 DNA helicase. Here, using human cellular models deficiency, we report that helicase prevents replication mediates homology-directed repair via homologous recombination. Mechanistically, promotes resection, enabling RPA RA...

A genetic screen of a population of Arabidopsis thaliana lines exhibiting enhanced somatic homologous recombination yielded a mutant affected in expression of a gene encoding a caltractin-like protein (centrin). The hyperrecombinogenic phenotype could be reproduced using RNA interference (RNAi) technology. Both the original mutant and the RNAi plants exhibited a moderate UV-C sensitivity as wel...

Double-strand break (DSB) repair is critical for maintaining genomic integrity and requires the processing of the 5' DSB ends. Recent studies have shed light on the mechanism and regulation of DNA end processing during DSB repair by homologous recombination.

Homologous recombination is a universal process, conserved from bacteriophage to human, which is important for the repair of double-strand DNA breaks. Recombination in mitochondrial DNA (mtDNA) was documented more than 4 decades ago, but the underlying molecular mechanism has remained elusive. Recent studies have revealed the presence of a Rad52-type recombination system of bacteriophage origin...