Breakage in breakage-fusion-bridge cycle: an 80-year-old mystery

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...

Fission is the division of a single entity into two or more parts, which regenerate into separate entities that resemble the original. Organisms in the Archaea and Bacteria domains reproduce using binary fission, in which a parent cell splits into two parts that can each grow to the size of the original parent cell. This asexual method of reproduction produces cells that are all genetically identical.

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:

Fatigue occurs when materials rupture under repeated or fluctuating loads, even at stress levels far below their static breaking strength. It typically results in brittle failure, even for ductile materials. It is a critical consideration in designing machines and structural components subjected to repetitive or varying loads. The nature of these loadings can range from fluctuating loads like unbalanced pump impellers causing vibrations to repeatedly bending a thin steel rod wire back and forth...