C hronic stalling of DNA replication forks by DNA damage such as UV irradiation, ionizing irradiation, chemicals, and reactive cellular metabolites impedes the progression of the cell cycle and eventually causes cell death. To circumvent such situations, cells have evolved the postreplication repair (PRR) pathway that bypasses DNA lesions to resolve stalled forks without removing the actual damage (1). In budding yeast Saccharomyces cerevisiae, PRR is carried out by 2 distinct pathways: translesion synthesis (TLS) and template switching (TS) (Fig. 1A). TLS uses multiple low-fidelity TLS polymerases to incorporate nucleotides across DNA lesions (2, 3). Switching from replicative polymerases ␦ or to TLS polymerases is promoted through the interaction between monoubiquitinated PCNA at lysine 164 (K164) and a ubiquitin-binding motif in TLS polymerases-a mechanism conserved from the budding yeast to human. The monoubiquitination of PCNA at K164 requires the RING-type ubiquitin ligase Rad18 (E3) and the ubiquitinconjugating enzyme Rad6 (E2).The TS pathway bypasses DNA damage by switching a stalled replicating end to the nascent daughter strand of the sister chromatid (1, 4). This pathway involves a lysine 63 (K63)-linked polyubiquitin chain that is further added onto the monoubiquitinated PCNA by Rad5 (E3) along with the Ubc13-Mms2 (E2 and E2 variant, respectively) heterodimer complex (Fig. 1 A). Distinct from the K48-linked polyubiquitination leading to protein degradation, the K63-linked polyubiquitination of PCNA is thought to promote TS in a proteasome-independent manner (5).The importance of the TLS pathway in the suppression of mammalian tumorigenesis emerged with the identification of a mutation in TLS polymerase in patients with the variant form of xeroderma pigmentosum and from studies with mouse models (6, 7). Despite the presence of UBC13 and MMS2 homologues in humans, the importance of the TS pathway is less clear in mammals because K63-linked polyubiquitination of PCNA, a hallmark event for the TS pathway, had not been observed until recently (8-10). We recently identified human SHPRH, which possesses SWI2/SNF2 and RING domains with similar architecture to the yeast Rad5 as a functional homologue of yeast Rad5 (9). Specifically, we demonstrated the in vivo activity of SHPRH in promoting a K63-linked polyubiquitination of PCNA as well as physical interactions of SHPRH with PCNA, RAD18, and UBC13. Depletion of SHPRH increases genomic instability after genotoxic stress. Consistent with our work, another study also demonstrated that SHPRH could polyubiquitinate PCNA in vitro (11).In the present study, we demonstrated that ectopic expression of HLTF/SMARCA3/RUSH/HIP116/Zbu1 (hereafter, HLTF) enhanced PCNA polyubiquitination in vivo. Depletion of SHPRH or HLTF significantly reduced polyubiquitination of chromatin-bound PCNA upon treatment of cells with DNA-damaging agents that cause stalled DNA replication forks. Furthermore, Hltf-deficient mouse embryonic fibroblasts (MEFs) showed elevated chromosome breaks an...

The body design with light weight and enhanced safety is a key issue in the car industry. Corresponding to this trend, POSCO is developing various automotive steel products with advanced performance. Conventional advanced high strength steels such as DP and TRIP steels are now expanding their application since the steels exhibit higher strength and ductility than those of conventional solution and precipitation strengthened high strength steels. Efforts have been made to enhance the mechanical performance of these steels such as ductility, hole expansion ratio, deep drawability, etc. Current research is focused on development of extra- and ultra-AHSS. Extra-AHSS are designed to utilize nano-scale retained austenite embedded in fine bainite and martensite. Ultra-AHSS are designed to have austenite as the major phase, and the ductility is enhanced primarily by continuous strain hardening generated during forming. These steels including extra- and ultra-AHSS are believed to be the next generation automotive steels which will replace the existing high strength steels due to their extremely high strength and ductility combinations.

Ultra-fine grained TRIP steels (UFG-TRIP) containing 6wt%Mn were produced by intercritical annealing. An ultra-fine grained microstructure with a grain size less than 1μm was obtained. The formation mechanism of the high volume fraction of retained austenite was investigated by dilatometry, XRD and magnetic saturation. The fraction of retained austenite was strongly dependent on the annealing temperature. The tensile properties were also found to be strongly influenced by the annealing temperature with poorer mechanical properties being observed at higher annealing temperatures. It was found that the stabilization of the retained austenite was both a composition and size-effect, made possible by the grain refinement due to the reversely transformed martensite.

The surface quality of steels containing solutes that have a strong affinity for oxygen can be markedly compromised during processing at elevated temperatures. Here, we examine a class of steels that are being developed for low density applications and hence, have relatively large concentrations of aluminium and manganese. These two elements compete for what little oxygen is available in the predominantly hydrogen–nitrogen mixture used to protect the steel during heat treatment. It is found that although the general sequence of oxidation does not seem to vary as the aluminium concentration is increased, the stoichiometry of the oxides changes. Manganese rich oxide is always the first to form for all the dew points examined, but is rapidly overtaken by aluminium oxide when the dew point is kept below −30°C. In the latter case, the eventual formation of an alumina film also halts the internal oxidation of aluminium. The results obtained using a variety of high resolution microscopy and analytical techniques have been analysed by calculating phase diagrams and by creating a finite difference model to reveal aspects of the internal oxidation problem.

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The microstructural evolution and the softening behavior of hot rolled and 60% cold rolled 0.85wt% carbon pearlitic steels during spheroidization annealing have been investigated by using the textural and microstructural information contained in the Orientation Imaging Microscopy (OIM) scans. The local boundary energy map, recently suggested by the present authors, is used to monitor the changes of stored plastic strain energy distribution in ferrite during the annealing process, which shows that the spheroidization process of cementite is finished before the completion of recrystallization of the 60% cold-rolled high carbon pearlitic steel.

Texture formation during an austempering treatment of a TRIP-assisted steel was studied by in-situ texture measurements with a high energy source (synchrotron). Samples from a cold rolled sheet were subjected to a complete heat treatment cycle for TRIP steels including reheating to the intercritical (α+γ) temperature region, isothermal soaking and bainitic holding (austempering) at 400°C for 600s. At specific points of the thermal cycle {200}γ, {220}γ {222}γ, {331}γ and {200}α, {211}α and {220}α Debye rings were recorded and the corresponding incomplete pole figures were calculated. The latter were used to derive the orientation distribution functions (ODFs) of BCC and FCC phases at specific steps of the annealing process after assuming the orthotropic sample symmetry. The acquired data for the texture evolution during the α–γ–α phase transformation showed that during the reheating for intercritical annealing the gamma phase with {011} orientation is among the first to nucleate from the recrystallized α phase during heating and the Goss and Cube orientations are among the principal gamma phase components which transform to BCC phase after cooling.

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