Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks.

Recruitment of 53BP1 to chromatin flanking double strand breaks (DSBs) requires γH2AX/MDC1/RNF8-dependent ubiquitination of chromatin and interaction of 53BP1 with histone H4 methylated on lysine 20 (H4K20me). Several histone methyltransferases have been implicated in 53BP1 recruitment, but their quantitative contributions to the 53BP1 response are unclear. We have developed a multi-photon laser (MPL) system to target DSBs to subfemtoliter nuclear volumes and used this to mathematically model DSB response kinetics of MDC1 and of 53BP1. In contrast to MDC1, which revealed first order kinetics, the 53BP1 MPL-DSB response is best fitted by a Gompertz growth function. The 53BP1 MPL response shows the expected dependency on MDC1 and RNF8. We determined the impact of altered H4K20 methylation on 53BP1 MPL response kinetics in mouse embryonic fibroblasts (MEFs) lacking key H4K20 histone methyltransferases. This revealed no major requirement for the known H4K20 dimethylases Suv4-20h1 and Suv4-20h2 in 53BP1 recruitment or DSB repair function, but a key role for the H4K20 monomethylase, PR-SET7. The histone methyltransferase MMSET/WHSC1 has recently been implicated in 53BP1 DSB recruitment. We found that WHSC1 homozygous mutant MEFs reveal an alteration in balance of H4K20 methylation patterns; however, 53BP1 DSB responses in these cells appear normal

Entanglement conditions for two-mode states: Applications

We examine the implications of several recently derived conditions [Hillery and Zubairy, Phys. Rev. Lett. 96, 050503 (2006)] for determining when a two-mode state is entangled. We first find examples of non-Gaussian states that satisfy these conditions. We then apply the entanglement conditions to the study of several linear devices, the beam splitter, the parametric amplifier, and the linear phase-insensitive amplifier. For the first two, we find conditions on the input states that guarantee that the output states are entangled. For the linear amplifier, we determine in the limit of high and no gain, when an entangled input leads to an entangled output. Finally, we show how application of two two-mode entanglement conditions to a three-mode state can serve as a test of genuine three-mode entanglement.Comment: 7 pages, no figures, replaced with published versio

Two-level laser light statistics

The statistics of the light emitted by two-level lasers is evaluated on the basis of generalized rate equations. According to that approach, all fluctuations are interpreted as being caused by the jumps that occur in active and detecting atoms. The intra-cavity Fano factor and the photo-current spectral density are obtained analytically for Poissonian and quiet pumps. The algebra is simple and the formulas hold for small as well as large pumping rates. Lasers exhibit excess noise at low pumping levels.Comment: 9 pages, 3 figures, in Optics Communication format (elsevier

BRCA1 and CtIP suppress long tract gene conversion between sister chromatids

BRCA1 controls early steps of the synthesis-dependent strand annealing (SDSA) pathway of homologous recombination, but has no known role following Rad51-mediated synapsis. Here we show that BRCA1 influences post-synaptic homologous recombination events, controlling the balance between short- (STGC) and long-tract gene conversion (LTGC) between sister chromatids. Brca1 mutant cells reveal a bias towards LTGC that is corrected by expression of wild type but not cancer-predisposing BRCA1 alleles. The LTGC bias is enhanced by depletion of CtIP but reversed by inhibition of 53BP1, implicating DNA end resection as a contributor to the STGC/LTGC balance. The impact of BRCA1/CtIP loss on the STGC/LTGC balance is abolished when the second (non-invading) end of the break is unable to support termination of STGC by homologous pairing (“annealing”). This suggests that BRCA1/CtIP-mediated processing of the second end of the break controls the annealing step that normally terminates SDSA, thereby suppressing the error-prone LTGC outcome

Rapid state purification protocols for a Cooper pair box

We propose techniques for implementing two different rapid state purification schemes, within the constraints present in a superconducting charge qubit system. Both schemes use a continuous measurement of charge (z) measurements, and seek to minimize the time required to purify the conditional state. Our methods are designed to make the purification process relatively insensitive to rotations about the x-axis, due to the Josephson tunnelling Hamiltonian. The first proposed method, based on the scheme of Jacobs [Phys. Rev. A 67, 030301(R) (2003)] uses the measurement results to control bias (z) pulses so as to rotate the Bloch vector onto the x-axis of the Bloch sphere. The second proposed method, based on the scheme of Wiseman and Ralph [New J. Phys. 8, 90 (2006)] uses a simple feedback protocol which tightly rotates the Bloch vector about an axis almost parallel with the measurement axis. We compare the performance of these and other techniques by a number of different measures.Comment: 14 pages, 14 figures. v2: Revised version after referee comments. Accepted for publication by Physical Review

BRCA1 controls homologous recombination at Tus/Ter-stalled mammalian replication forks

Replication fork stalling can promote genomic instability, predisposing to cancer and other diseases1–3. Stalled replication forks may be processed by sister chromatid recombination (SCR), generating error-free or error-prone homologous recombination (HR) outcomes4–8. In mammalian cells, a long-standing hypothesis proposes that the major hereditary breast/ovarian cancer predisposition gene products, BRCA1 and BRCA2, control HR/SCR at stalled replication forks9. Although BRCA1 and BRCA2 affect replication fork processing10–12, direct evidence that BRCA genes regulate HR at stalled chromosomal replication forks is lacking due to a dearth of tools for studying this process. We report that the Escherichia coli Tus/Ter complex13–16 can be engineered to induce site-specific replication fork stalling and chromosomal HR/SCR in mammalian cells. Tus/Ter-induced HR entails processing of bidirectionally arrested forks. We find that the BRCA1 C-terminal tandem BRCT repeat and regions of BRCA1 encoded by exon 11—two BRCA1 elements implicated in tumor suppression—control Tus/Ter-induced HR. Inactivation of either BRCA1 or BRCA2 increases the absolute frequency of “long-tract” gene conversions at Tus/Ter-stalled forks—an outcome not observed in response to a restriction endonuclease-mediated chromosomal double strand break (DSB). Therefore, HR at stalled forks is regulated differently from HR at DSBs arising independently of a fork. We propose that aberrant long-tract HR at stalled replication forks contributes to genomic instability and breast/ovarian cancer predisposition in BRCA mutant cells

Uncertainty characteristics of generalized quantum measurements

The effects of any quantum measurement can be described by a collection of measurement operators {M_m} acting on the quantum state of the measured system. However, the Hilbert space formalism tends to obscure the relationship between the measurement results and the physical properties of the measured system. In this paper, a characterization of measurement operators in terms of measurement resolution and disturbance is developed. It is then possible to formulate uncertainty relations for the measurement process that are valid for arbitrary input states. The motivation of these concepts is explained from a quantum communication viewpoint. It is shown that the intuitive interpretation of uncertainty as a relation between measurement resolution and disturbance provides a valid description of measurement back action. Possible applications to quantum cryptography, quantum cloning, and teleportation are discussed.Comment: 8 pages, small additions on cloning and on definitions of delta A_mf, et

Spectroscopy of a Cooper-Pair box in the Autler-Townes configuration

A theoretical spectroscopic analysis of a microwave driven superconducting charge qubit (Cooper-pair box coupled) to an RLC oscillator model is performed. By treating the oscillator as a probe through the backreaction effect of the qubit on the oscillator circuit, we extract frequency splitting features analogous to the Autler-Townes effect from quantum optics, thereby extending the analogies between superconducting and quantum optical phenomenology. These features are found in a frequency band that avoids the need for high frequency measurement systems and therefore may be of use in qubit characterization and coupling schemes. In addition we find this frequency band can be adjusted to suit an experimental frequency regime by changing the oscillator frequency.Comment: 13 pages, 7 figures. v2: Revised version after referee comments. Accepted for publication by Physical Review