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Fragile sites are chromosomal regions that are susceptible to gaps or breaks. Common fragile sites occur in all individuals, are thought to be sensitive to replication stress due to chromosome structure, and are often re-arranged in cancer. Rare fragile sites are caused by nucleotide repeats and are inherited.
Epstein–Barr Virus (EBV) nuclear antigen 1 is shown to induce breakage of a fragile site on chromosome 11 by binding to a cluster of EBV-like imperfect palindromic repeats.
Here, the authors show that common fragile sites are unstable under loose activation of the DNA-replication checkpoint. Tight checkpoint activation or CDK1 inhibition stabilizes them by advancing completion of their replication via extra replication-initiation events that are dependent on S-phase availability of proteins involved in pre-RC building.
Profiling of human DNA polymerase Polε and Polα demonstrates their roles in leading and lagging strand DNA synthesis, and their independent measures allowed accurate predictions of replication dynamics and effects of transcription.
G-quadruplex (G4) can be formed in telomeric DNA. Here the authors show that BRCA2 interacts with telomere G4 structure generated during telomere replication, protecting telomere from nuclease attack.
This protocol describes enrichment of telomeric repeats from human and mouse cells by successive rounds of restriction digestion and size fractionation, resulting in high-quality preparations suitable for single-molecule and structural studies.
BRCA1-mediated resolution of R-loops has previously been described. Here the authors reveal a functional association of BRCA1 with TERRA RNA at telomeres, which develops in an R-loop-, and a cell cycle-dependent manner.
A cardinal rule of DNA replication is to prevent any possibility of pre-replication complexes re-loading during S phase, risking genotoxic over-replication. But can this rule be broken in emergency situations to preserve genome integrity?
Poly(dA:dT) tracts characterize strong DNA replication origins in mammals and cause replication-fork collapse and DNA breaks that underlie the expression of fragile sites.
The suppression of homologous recombination in G1 depends on BRCA1–PALB2–BRCA2 complex formation at sites of damage. In mitosis, DNA repair factors prevent the formation of DNA damage by facilitating mitotic replication.
