Association between RAD51gene polymorphism rs1801321 and ovarian cancer risk

Ovarian cancer is one of the most common gynecological malignancies. The gene RAD51involves homologous recombinational repair for double-strand breaks of DNA, so its polymorphisms and mutations are associated with cancer risk. The authors studied, by using a case-control design, whether single nucleotide polymorphism rs1801321 of RAD51 gene associated with ovarian cancer risk among Vietnamese females. Sample sets included 380 ovarian cancer cases and 380 healthy controls of similar age distribution. The genotypes of rs1801321 polymorphism were determined using the Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The distribution of genotype GG, GT, TT was 55.3, 29.2, 15.5% for the patients group and 47.9, 41.8, 10.3% for the control group, respectively (p=0.001). The RAD51 rs1801321 polymorphism was associated with the risk of ovarian cancer among Vietnamese females.

Genetic Susceptibility to Endometrial Cancer: Risk Factors and Clinical Management

Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a subgroup of patients belongs to cancer predisposition syndromes (most notably the Lynch Syndrome) with high to intermediate lifetime risks, there are also several common genomic polymorphisms contributing to the spectrum of germline predispositions. Germline variants and somatic events may act in concert to modulate the molecular evolution of the tumor, where mismatch-repair deficiency is common in endometrioid endometrial tumors whereas homologous recombinational repair deficiency has been described for non-endometrioid endometrial tumors. In this review, we will survey the currently known genomic predispositions for endometrial cancer and discuss their relevance for clinical management in terms of counseling, screening and novel treatments.

RecO impedes RecG-SSB binding to impair the strand annealing recombination pathway in E.coli

Faithful duplication of genomic DNA relies not only on the fidelity of DNA replication itself, but also on fully functional DNA repair and homologous recombination machinery. We report a molecular mechanism responsible for deciding homologous recombinational repair pathways during replication dictated by binding of RecO and RecG to SSB in E.coli. Using a RecG-yfp fusion protein, we found that RecG-yfp foci appeared only in the ΔrecG, ΔrecO and ΔrecA, ΔrecO double mutants. Surprisingly, foci were not observed in wild-type ΔrecG, or double mutants where recG and either recF or, separately recR were deleted. In addition, formation of RecG-yfp foci in the ΔrecO::kanR required wildtype ssb, as ssb-113 could not substitute. This suggests that RecG and RecO binding to SSB is competitive. We also found that the UV resistance of recO alone mutant increased to certain extent by supplementing RecG. In an ssb-113 mutant, RecO and RecG worked following a different pattern. Both RecO and RecG were able to participate in repairing UV damages when grown at permissive temperature, while they could also be involved in making DNA double strand breaks when grown at nonpermissive temperature. So, our results suggested that differential binding of RecG and RecO to SSB in a DNA replication fork in Escherichia coli.may be involved in determining whether the SDSA or DSBR pathway of homologous recombinational repair is used.Author summarySingle strand DNA binding proteins (SSB) stabilize DNA holoenzyme and prevent single strand DNA from folding into non-B DNA structures in a DNA replication fork. It has also been revealed that SSB can also act as a platform for some proteins working in DNA repair and recombination to access DNA molecules when DNA replication fork needs to be reestablished. In Escherichia coli, several proteins working primarily in DNA repair and recombination were found to participate in DNA replication fork resumption by physically interacting with SSB, including RecO and RecG etc. However the hierarchy of these proteins interacting with SSB in Escherichia coli has not been well defined. In this study, we demonstrated a differential binding of RecO and RecG to SSB in DNA replication was used to establish a RecO-dependent pathway of replication fork repair by abolishing a RecG-dependent replication fork repair. We also show that, RecG and RecO could randomly participate in DNA replication repair in the absence of a functional SSB, which may be responsible for the generation of DNA double strand breaks in an ssb-113 mutant in Escherichia coli.

Matrin3 promotes homologous recombinational repair by regulation of RAD51

Matrin3 is a highly conserved inner nuclear matrix protein involved in multiple stages of RNA metabolism. Although Matrin3 may also play a role in DNA repair, its precise roles have remained unclear. In this study, we showed that the depletion of Matrin3 led to decreased homologous recombination (HR) efficiency and increased radiation sensitivity of cells. Matrin3-depleted cells showed impaired DNA damage-dependent focus formation of RAD51, a key protein in HR. These findings suggest that Matrin3 promotes HR by regulating RAD51.

The evolution of meiotic sex and its alternatives

Meiosis is an ancestral, highly conserved process in eukaryotic life cycles, and for all eukaryotes the shared component of sexual reproduction. The benefits and functions of meiosis, however, are still under discussion, especially considering the costs of meiotic sex. To get a novel view on this old problem, we filter out the most conserved elements of meiosis itself by reviewing the various modifications and alterations of modes of reproduction. Our rationale is that the indispensable steps of meiosis for viability of offspring would be maintained by strong selection, while dispensable steps would be variable. We review evolutionary origin and processes in normal meiosis, restitutional meiosis, polyploidization and the alterations of meiosis in forms of uniparental reproduction (apomixis, apomictic parthenogenesis, automixis, selfing) with a focus on plants and animals. This overview suggests that homologue pairing, double-strand break formation and homologous recombinational repair at prophase I are the least dispensable elements, and they are more likely optimized for repair of oxidative DNA damage rather than for recombination. Segregation, ploidy reduction and also a biparental genome contribution can be skipped for many generations. The evidence supports the theory that the primary function of meiosis is DNA restoration rather than recombination.

Structure of the human DNA-repair protein RAD52 containing surface mutations

The Rad52 protein is a eukaryotic single-strand DNA-annealing protein that is involved in the homologous recombinational repair of DNA double-strand breaks. The isolated N-terminal half of the human RAD52 protein (RAD521–212) forms an undecameric ring structure with a surface that is mostly positively charged. In the present study, it was found that RAD521–212containing alanine mutations of the charged surface residues (Lys102, Lys133 and Glu202) is highly amenable to crystallization. The structure of the mutant RAD521–212was solved at 2.4 Å resolution. The structure revealed an association between the symmetry-related RAD521–212rings, in which a partially unfolded, C-terminal region of RAD52 extended into the DNA-binding groove of the neighbouring ring in the crystal. The alanine mutations probably reduced the surface entropy of the RAD521–212ring and stabilized the ring–ring association observed in the crystal.