Homologous recombination is a process in which DNA molecules exchange portions of their genetic material with each other. It can be thought of as a DNA "swap" between two similar DNA strands. This process plays a crucial role in repairing damaged DNA, creating genetic diversity, and ensuring proper chromosome segregation during cell division.
Full definition
Indeed, at least in part, the abnormalities
in homologous recombination deficiency have contributed to the very outstanding responses to platinum therapy and very striking new data with PARP (poly [ADP - ribose] polymerase) inhibitors.
Caris performed the molecular profiling on 48,733 solid tumor samples to assess the prevalence of
homologous recombination deficiency in about 20 different types of solid tumors.
Lack of functional wild - type BRCA2 is associated with defects in the repair of double - strand DNA breaks using
homologous recombination repair (HRR) and with a characteristic mutational spectrum (6, 7).
But BRCA is just one of the many genes that encode important proteins in the DNA repair pathway known
as homologous recombination,» says the study's lead author, Arielle Heeke, MD, a clinical fellow at Georgetown Lombardi Comprehensive Cancer Center.
The trial «Niraparib Plus Carboplatin in Patients
with Homologous Recombination Deficient Advanced Solid Tumor Malignancies» is not yet recruiting patients for enrollment.
However, while CRISPR is remarkably effective for introducing non-sequence specific frameshift mutations through aberrant double strand break repair, it has proven more challenging to develop high efficiency CRISPR - based approaches for the generation of knockins
via homologous recombination with a homologous repair template.
from the University of Washington reported a surprising finding - when delivered via AAV infection, gene targeting vectors with relatively short (1 kb) homology arms
underwent homologous recombination at a frequency three orders of magnitude higher than identical targeting vectors delivered through transfection of naked DNA
Their findings in the study «Phosphoglycerate mutase 1 regulates dNTP pool and
promotes homologous recombination repair in cancer cells,» which has been published in The Journal of Cell Biology, suggest that this FDA - approved ovarian cancer medicine has the potential to treat a wider range of cancer types than currently indicated.
In that year, Russell and Hirata from the University of Washington reported a surprising finding - when delivered via AAV infection, gene targeting vectors with relatively short (1 kb) homology arms underwent
homologous recombination at a frequency three orders of magnitude higher than identical targeting vectors delivered through transfection of naked DNA.
Median progression - free survival with niraparib compared to placebo was 21.0 vs 5.5 months in the germline BRCA mutation group (hazard ratio [HR] 0.27, 95 % confidence interval [CI] 0.173 to 0.410, p < 0.0001), 9.3 months vs 3.9 months in the non-germline BRCA mutation group (HR 0.45, 95 % CI 0.338 to 0.607, p < 0.0001), and 12.9 vs 3.8 months in a subgroup of the non-mutation cohort who had
homologous recombination DNA repair deficiencies (HRD)(HR 0.38, 95 % CI 0.243 to 0.586, p < 0.0001).
Cells lacking the BRCA1 ubiquitin ligase activity were found to be sensitive to certain DNA damaging agents that
need homologous recombination in for repair.
But
if homologous recombination could be worked out in human (embryonic) stem cells, then cardiomyocytes with mutations in ion channels could be derived, as well as a large number of other very useful disease models of other tissues.
Mice generated from embryonic stem cells in which ion channel genes have been mutated by
homologous recombination often have a perfectly normal heart.
The marriage of Professors Capecchi and Smithies»
homologous recombination technique with Sir Martin's stem cell discoveries has created the highly versatile new technology of gene targeting.
Moreover, as transposons quickly accumulate the probability of deletions through non-allelic
homologous recombination also increases, counteracting their initial impact on genome growth [11, 12].
As part of our coverage of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2 — 6 in Chicago, we are speaking with Gordon Mills, MD, PhD, chair of the department of systems biology and professor of medicine and immunology at the University of Texas MD Anderson Cancer Center in Houston, about ways to
incorporate homologous recombination markers into clinical practice for ovarian cancer.
Patients with
positive homologous recombination deficiency (HRD) status had a median PFS of 13.6 months with rucaparib, compared with 5.4 months with placebo, for an HR of 0.32 (95 % CI, 0.24 — 0.42; P <.0001).
Maresca, M., Erler, A., Fu, J., Friedrich, A., Zhang, Y. and Stewart, A. F. Single - stranded heteroduplex intermediates in lambda
Red homologous recombination.
A second DNA binding site in human BRCA2 promotes
homologous recombination Catharina von Nicolai, Åsa Ehlén, Charlotte Martin, Xiaodong Zhang & Aura Carreira Nature Communications 7, Article number: 12813 (2016), doi: 10.1038 / ncomms12813
By combining CRISPR / Cas9 editing technology with the
yeast homologous recombination machinery, genome transplantation and other tools developed by the JCVI / SGI team, the group has developed an efficient, high throughput platform to test engineered essential genes like the 16S rRNA thus facilitating more experiments into biological function and helping to answer basic questions of life.