DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin

DNA double-strand breaks (DSBs) can induce chromosomal aberrations and carcinogenesis and their correct repair is crucial for genetic stability. The cellular response to DSBs depends on damage signaling including the phosphorylation of the histone H2AX (γH2AX). However, a lack of γH2AX formation in heterochromatin (HC) is generally observed after DNA damage induction. Here, we examine γH2AX and repair protein foci along linear ion tracks traversing heterochromatic regions in human or murine cells and find the DSBs and damage signal streaks bending around highly compacted DNA. Given the linear particle path, such bending indicates a relocation of damage from the initial induction site to the periphery of HC. Real-time imaging of the repair protein GFP-XRCC1 confirms fast recruitment to heterochromatic lesions inside murine chromocenters. Using single-ion microirradiation to induce localized DSBs directly within chromocenters, we demonstrate that H2AX is early phosphorylated within HC, but the damage site is subsequently expelled from the center to the periphery of chromocenters within ∼20 min. While this process can occur in the absence of ATM kinase, the repair of DSBs bordering HC requires the protein. Finally, we describe a local decondensation of HC at the sites of ion hits, potentially allowing for DSB movement via physical forces

DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin

DNA double-strand breaks (DSBs) can induce chromosomal aberrations and carcinogenesis and their correct repair is crucial for genetic stability. The cellular response to DSBs depends on damage signaling including the phosphorylation of the histone H2AX (γH2AX). However, a lack of γH2AX formation in heterochromatin (HC) is generally observed after DNA damage induction. Here, we examine γH2AX and repair protein foci along linear ion tracks traversing heterochromatic regions in human or murine cells and find the DSBs and damage signal streaks bending around highly compacted DNA. Given the linear particle path, such bending indicates a relocation of damage from the initial induction site to the periphery of HC. Real-time imaging of the repair protein GFP-XRCC1 confirms fast recruitment to heterochromatic lesions inside murine chromocenters. Using single-ion microirradiation to induce localized DSBs directly within chromocenters, we demonstrate that H2AX is early phosphorylated within HC, but the damage site is subsequently expelled from the center to the periphery of chromocenters within ∼20 min. While this process can occur in the absence of ATM kinase, the repair of DSBs bordering HC requires the protein. Finally, we describe a local decondensation of HC at the sites of ion hits, potentially allowing for DSB movement via physical forces

In situ measurement of mechanical vibrations of a 4-rod RFQ at GSI

A new 4-rod RFQ was commissioned at the UNILAC in 2009, it went into operation in 2010. At high rf amplitudes strong modulations of the rf reflection emerge. They are attributed to mechanical oscillations of the rods, excited by the rf pulse. As these modulations could so far only be seen during the rf pulse by means of rf measurements, a direct observation of the mechanical vibrations was desirable. Such measurements have been conducted using a commercial laser vibrometer, allowing the investigation of the mechanical behavior of the RFQ in situ and independent of the presence of rf power. Results from investigations under standard operation conditions confirm the vibrations as the source of the modulations observed by rf as well as their excitation by the rf pulse. Further measurements revealed more details about the excitation process, leading to a better understanding and possibly new ways of mitigation.Comment: Proc. LINAC 2014, TUPP057; 4 pages, 5 figures; JACoW-GSI-2013.cls, should also work with jacow.cls as of Dec. 201

In situ measurement of mechanical vibrations of a 4-rod RFQ at GSI

Soft clays in coastal areas have low shear strength and high compressibility. Consequently, certain construction activities for infrastructure developments in these deposits often pose geotechnical problems due to large time-dependent settlements and lateral movements. Ground improvement techniques are adopted in such terrains to reduce the water content of soft clays by preloading with surcharge fill over vertical drains. Depending on the magnitude of the surcharge load used, substantial immediate settlement with lateral movements can take place during preloading, leading to undrained stability problems in various parts of the clay foundation. Therefore, the use of vacuum-assisted preloading has now become a popular method in ground improvement works where substantial loads need to be carried out to meet a desired rate of settlement and mitigate undrained failure by controlling lateral displacements. To assist the vacuum propagation to significant depths, vertical drains are used in tandem at the Port of Brisbane, Australia, and vacuum-assisted surcharge preloading and conventional surcharge preloading schemes were adopted to reduce the consolidation time and long-term settlement in soft Holocene clays in 2009. It is shown that a combined vacuum surcharge loading system with a standard surcharge fill highlights the obvious benefits of vacuum consolidation in reducing long-term settlement and enhanced stability