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Whether homologous recombination or NHEJ is used to repair double-strand breaks is largely determined by the phase of cell cycle. Homologous recombination repairs DNA before the cell enters mitosis (M phase). It occurs during and shortly after DNA replication, in the S and G 2 phases of the cell cycle, when sister chromatids are more easily ...
Poly (ADP ribose) polymerase (PARP) inhibitors are designed to treat BRCA1- and BRCA2- defect tumors owing to their homologous recombination deficiency. [4] These drugs have been majorly implemented in breast and ovarian cancers, [ 5 ] and their clinical efficacy among patients with other types of cancers, such as pancreatic cancer, is still ...
In October 2019, the indication for niraparib was expanded to include people with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status. [8] HRD is defined by either a deleterious or ...
Homologous recombination deficiency (HRD): DNA double-strand break requires homologous recombination mechanism for accurate repair of breakpoints. DNA mismatch repair (MMR) deficiency: The mismatch repair machinery recognizes and repairs erroneous base pair insertion, deletion or mis-incorporation.
Homologous recombination: lack of Zmpste24 prevents lamin A formation and causes progeroid phenotypes in mice and humans, increased DNA damage and chromosome aberrations, sensitivity to DNA-damaging agents and deficiency in homologous recombination [36]
Bowtell [67] reviewed the literature indicating that deficient homologous recombination repair caused by BRCA1 deficiency is tumorigenic. In particular this deficiency initiates a cascade of molecular events that sculpt the evolution of high-grade serous ovarian cancer and dictate its response to therapy.
The most common form of HDR is homologous recombination. The HDR mechanism can only be used by the cell when there is a homologous piece of DNA present in the nucleus, mostly in G2 and S phase of the cell cycle. Other examples of homology-directed repair include single-strand annealing and breakage-induced replication.
Here, homologous recombination (HR) can, in principle, provide specificity to the integration process, but for eukaryotes it is compromised by an extremely low efficiency. Although meganucleases, zinc-finger- and transcription activator-like effector nucleases (ZFNs and TALENs) are actual tools supporting HR, it was the availability of site ...