Repair of DNA double-strand breaks (DSBs) protects cells and organisms, as well as their genome integrity. Since DSB repair occurs in the context of chromatin, chromatin must be modified to prevent it from inhibiting DSB repair. Evidence supports the role of histone modifications and ATP-dependent chromatin remodeling in repair and signaling of chromosome DSBs. The key questions are, then, what...

In bacteria, double-strand break (DSB) repair via homologous recombination is thought to be initiated through the bi-directional degradation and resection of DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has been well-studied in vitro, with translocation speeds between 400-2000 bp/s on linear DNA suggesting that a large section of DNA around a break site is proces...

Homologous recombination (HR) is essential for cellular survival in mammals. In this review, the substrates for HR, the pathways of repair, and their end products (i.e. sister chromatid exchange (SCE), gene conversion, deletions or tandem duplications) are discussed. HR is involved in the repair of DNA double-strand breaks (DSBs) and DNA lesions that occur at replication forks. A classical DSB ...

S-phase cyclin-dependent kinase Cdc28-Clb5 (CDK-S) and Dbf4-dependent kinase Cdc7-Dbf4 (DDK) are highly conserved kinases well known for their roles in the initiation of DNA replication. CDK-S is also essential for initiation of meiotic recombination because it phosphorylates Ser30 of Mer2, a meiosis-specific double-strand break (DSB) protein. This work shows that the phosphorylation of Mer2 Se...

Improper DNA double-strand break (DSB) repair results in complex genomic rearrangements (CGRs) in many cancers and various congenital disorders in humans. Trinucleotide repeat sequences, such as (GAA)n repeats in Friedreich's ataxia, (CTG)n repeats in myotonic dystrophy, and (CGG)n repeats in fragile X syndrome, are also subject to double-strand breaks within the repetitive tract followed by DN...

In yeast, broken chromosomes can be repaired by recombination, resulting in nonreciprocal translocations. In haploid cells suffering an HO endonuclease-induced, double-strand break (DSB), nearly 2% of the broken chromosome ends recombined with a sequence near the opposite chromosome end, which shares only 72 bp of homology with the cut sequence. This produced a repaired chromosome with the same...

Bloom's helicase (BLM) is thought to prevent crossing-over during DNA double-strand-break repair (DSBR) by disassembling double-Holliday junctions (dHJs) or by preventing their formation. We show that the Saccharomyces cerevisiae BLM ortholog, Sgs1, prevents aberrant crossing-over during meiosis by suppressing formation of joint molecules (JMs) comprising three and four interconnected duplexes....

To distinguish among possible mechanisms of repair of a double-strand break (DSB) by gene conversion in budding yeast, Saccharomyces cerevisiae, we employed isotope density transfer to analyze budding yeast mating type (MAT) gene switching in G2/M-arrested cells. Both of the newly synthesized DNA strands created during gene conversion are found at the repaired locus, leaving the donor unchanged...

The DNA double-strand break (DSB) is the principle cytotoxic lesion for ionizing radiation and radio-mimetic chemicals but can also be caused by mechanical stress on chromosomes or when a replicative DNA polymerase encounters a DNA single-strand break or other type of DNA lesion. DSBs also occur as intermediates in various biological events, such as V(D)J recombination in developing lymphoid ce...