"Replication forks" refers to the points in DNA where the molecule is being copied or replicated. It's like a fork in the road where the DNA splits into two strands, and each strand serves as a template for creating a new copy of the original DNA molecule.
Full definition
Characterizing the molecular pathways regulating genomic stability at
damaged replication forks in HR - deficient cancers will increase our understanding of the cellular response to replicative stress, and in the same time, potentially allow the identification of new predictors (biomarkers) of chemo - sensitivity / resistance in these tumors (Figure 2B).
This allows us to determine the fractions of rightward -(R) and leftward -(L) moving forks at each locus, and to construct the complete profiles
of replication fork directionality (RFD = R - L) along the genome.
Moreover, REV1L is involved with the recruitment of DNA polymerase eta to assist in DNA replication at arrested
replication forks in areas of DNA lesions such as those formed by thymine dimmers [35, 36].
BRCA1 / 2 proteins function in homologous recombination (HR)- mediated DNA repair and cooperate with Fanconi anemia (FA) proteins to maintain genomic integrity through
replication fork stabilization.
The complex between the DnaB helicase and the DnaG primase unwinds duplex DNA at the
eubacterial replication fork and synthesizes the Okazaki RNA primers.
«This is because while both cell types show hydroxyurea - induced gene expression, collision with replication occurs differentially
because replication forks have progressed to different extent in these cells,» said Feng.
Feng said that breakage patterns at different subsets of the hydroxyurea - induced genes were also observed in wild type cells and checkpoint - deficient mutant cells with
unstable replication forks.
In addition, repair of DSBs contribute to the stabilization of
damaged replication forks (RFs), that recently emerged as a central process that controls genomic stability and promotes chemoresistance.
During this stage,
the replication forks can meet obstacles that cause their blockage or even the appearance of breaks in the DNA.
In this project, it was shown that Rrm3, a protein that travels beside
the replication forks, has a role in this process of repair by recombination, so avoiding genetic instability.
These results reveal a synthetic lethal relationship between FANCD2 and BRCA1 / 2, and they identify FANCD2 as a central player orchestrating DNA repair pathway choice at
the replication fork.
HRR - deficient tumors show increased sensitivity to drugs such as platinum salts and inhibitors of the DNA repair protein PARP1 (PARPi) that induce double - strand breaks by stalling
replication forks and causing replication fork collapse (8, 9).
For instance, classical and alternative pathways interplay and compete for the repair of DSBs occurring during replication (i.e. damaged
replication forks)(Figure 1B).