Radiation-induced Assembly of Rad51 and Rad52 Recombination Complex Requires ATM and c-Abl

Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c-Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R-induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I-R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct post-translational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R

Analysis and Numerical Simulation of Hydrofracture Crack Propagation in Coal-Rock Bed

In underground coal mines, hydrofracture can cause the increase of breathability in the fractured coal bed. When the hydrofracture crack propagates to the interface between the coal bed and the roof-floor stratum, the crack may enter roof-floor lithology, thus posing a limit on the scope of breathability increase and making it difficult to support the roof and floor board for subsequent coal mining. In this work, a two-dimensional model of coal rock bed that contains hydrofracture crack was constructed. Then an investigation that combines the fracture mechanics and the system of flow and solid in rock failure process analysis (RFPA2D-Flow) were carried out to study the failure mechanism at the interface between rocks and coals, and critical water pressure that hydrofracture crack propagates. The results indicated that the main factors that affect the direction of hydrofracture crack propagation are the angle of intersection between coal-rock interface and horizontal section, horizontal crustal stress difference, tension-shear mixed crack fracture toughness in coal-rock interface and differences in elasticity modulus of coal-rock bed.The possibility of crack directly entering coal-rock interface would increase with the increase in angle of intersection or horizontal crustal stress difference. The trend that crack propagates along the coal-rock interface will become stronger with the decrease of the fracture toughness at the coal-rock interface and the increase of the elasticity modulus difference between the coal bed and the roof strata. The results of this study was to put forward a method of controlling hydrofracture crack, optimize the fracturing well location provides a certain theoretical basis

The Ultraviolet Damage Endonuclease (UVDE) Protein and Alternative Excision Repair: A Highly Diverse System for Damage Recognition and Processing

https://nsuworks.nova.edu/hpd_md_facbooks/1003/thumbnail.jp

The Ultraviolet Damage Endonuclease (UVDE) Protein and Alternative Excision Repair: A Highly Diverse System for Damage Recognition and Processing

https://nsuworks.nova.edu/hpd_com_facbooks/1041/thumbnail.jp

Characterization of AP lyase activities of Saccharomyces cerevisiae Ntg1p and Ntg2p: implications for biological function

Saccharomyces cerevisiae possesses two Escherichia coli endonuclease III homologs, NTG1 and NTG2, whose gene products function in the base excision repair pathway and initiate removal of a variety of oxidized pyrimidines from DNA. Although the glycosylase activity of these proteins has been well studied, the in vivo importance of the AP lyase activity has not been determined. Previous genetic studies have suggested that the AP lyase activities of Ntg1p and Ntg2p may be major contributors in the initial processing of abasic sites. We conducted a biochemical characterization of the AP lyase activities of Ntg1p and Ntg2p via a series of kinetic experiments. Such studies were designed to determine if Ntg1p and Ntg2p prefer specific bases located opposite abasic sites and whether these lesions are processed with a catalytic efficiency similar to Apn1p, the major hydrolytic AP endonuclease of yeast. Our results indicate that Ntg1p and Ntg2p are equally effective in processing four types of abasic site-containing substrates. Certain abasic site substrates were processed with greater catalytic efficiency than others, a situation similar to Apn1p processing of such substrates. These biochemical studies strongly support an important biological role for Ntg1p and Ntg2p in the initial processing of abasic sites and maintenance of genomic stability