38 research outputs found
Protein phosphatase 1 acts as a RIF1 effector to suppress DSB resection prior to Shieldin action
Funding Information: We thank K. Murakami, H. Kimura, H. Kurumizaka, and J.M. Stark for materials. This work was supported by JSPS KAKENHI grant nos. JP19H03156 , JP18H04713 , JP18H05532 , and JP25116004 (to C.O.), JP17H06426 (to K.N.), JP18H04900 and JP19H04267 (to H.S.), the Mitsubishi Foundation (to H.S.), and by Cancer Research UK awards C1445/A19059 and DRCPGM/100013 (to S.H. and A.D.D. lab). Publisher Copyright: © 2021 The Author(s)Peer reviewedPublisher PD
Magnetic Reynolds number dependence of reconnection rate and flow structure of the self-similar evolution model of fast magnetic reconnection
This paper investigates Magnetic Reynolds number dependence of the
``self-similar evolution model'' (Nitta et al. 2001) of fast magnetic
reconnection. I focused my attention on the flow structure inside and around
the reconnection outflow, which is essential to determine the entire
reconnection system (Nitta et al. 2002). The outflow is consist of several
regions divided by discontinuities, e.g., shocks, and it can be treated by a
shock-tube approximation (Nitta 2004). By solving the junction conditions
(e.g., Rankine-Hugoniot condition), the structure of the reconnection outflow
is obtained. Magnetic reconnection in most astrophysical problems is
characterized by a huge dynamic range of its expansion ( for typical
solar flares) in a free space which is free from any influence of external
circumstances. Such evolution results in a spontaneous self-similar expansion
which is controlled by two intrinsic parameters: the plasma- and the
magnetic Reynolds number. The plasma- dependence had been investigated in
our previous paper. This paper newly clarifies the relation between the
reconnection rate and the inflow structure just outside the Petschek-like slow
shock: As the magnetic Reynolds number increases, strongly converging inflow
toward the Petschek-like slow shock forms, and it significantly reduces the
reconnection rate.Comment: 16 pages. to appear in ApJ (2006 Jan. 20 issue
BRCA1 Directs the Repair Pathway to Homologous Recombination by Promoting 53BP1 Dephosphorylation
Summary: BRCA1 promotes homologous recombination (HR) by activating DNA-end resection. By contrast, 53BP1 forms a barrier that inhibits DNA-end resection. Here, we show that BRCA1 promotes DNA-end resection by relieving the 53BP1-dependent barrier. We show that 53BP1 is phosphorylated by ATM in S/G2 phase, promoting RIF1 recruitment, which inhibits resection. 53BP1 is promptly dephosphorylated and RIF1 released, despite remaining unrepaired DNA double-strand breaks (DSBs). When resection is impaired by CtIP/MRE11 endonuclease inhibition, 53BP1 phosphorylation and RIF1 are sustained due to ongoing ATM signaling. BRCA1 depletion also sustains 53BP1 phosphorylation and RIF1 recruitment. We identify the phosphatase PP4C as having a major role in 53BP1 dephosphorylation and RIF1 release. BRCA1 or PP4C depletion impairs 53BP1 repositioning, EXO1 recruitment, and HR progression. 53BP1 or RIF1 depletion restores resection, RAD51 loading, and HR in PP4C-depleted cells. Our findings suggest that BRCA1 promotes PP4C-dependent 53BP1 dephosphorylation and RIF1 release, directing repair toward HR. : Following induction of DNA double-strand break, a pro-end-joining environment is created in G2 by transient 53BP1 phosphorylation and RIF1 recruitment. Here, Isono et al. show that, if timely repair does not ensue, BRCA1 promotes 53BP1 dephosphorylation and RIF1 release, favoring repair by homologous recombination. Keywords: ATM, DNA-end resection, BRCA1, 53BP1, RIF1, PP4C, NHEJ, H
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
Wnt signaling in triple-negative breast cancer
Wnt signaling regulates a variety of cellular processes, including cell fate, differentiation, proliferation and stem cell pluripotency. Aberrant Wnt signaling is a hallmark of many cancers. An aggressive subtype of breast cancer, known as triple-negative breast cancer (TNBC), demonstrates dysregulation in canonical and non-canonical Wnt signaling. In this review, we summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of TNBC. We review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease
Inhibition of RIF1 by SCAI Allows BRCA1-Mediated Repair
DNA double-strand breaks (DSBs) are repaired by either the homology-directed repair (HDR) or the non-homologous end-joining (NHEJ) pathway. RIF1 (RAP1-interacting factor homolog) was recently shown to stimulate NHEJ through an interaction with 53BP1 (p53-binding protein 1) phosphorylated at S/TQ sites, but the molecular mechanism underlying pathway choice remains unclear. Here, we show that SCAI (suppressor of cancer cell invasion) binds to 53BP1 phosphorylated at S/TP sites and facilitates HDR. Upon DNA damage, RIF1 immediately accumulates at damage sites and then gradually dissociates from 53BP1 and is subsequently replaced with SCAI. Depletion of SCAI reduces both the accumulation of HDR factors, including BRCA1 (breast cancer susceptibility gene 1), at damage sites and the efficiency of HDR, as detected by a reporter assay system. These data suggest that SCAI inhibits RIF1 function to allow BRCA1-mediated repair, which possibly includes alt-NHEJ and resection-dependent NHEJ in G1, as well as HDR in S/G2
The embryo as moral work object: PGD/IVF staff views and experiences
Copyright @ 2008 the authors. This article is available in accordance with the Creative Commons Deed, Attribution 2.5, see http://creativecommons.org/licenses/by-nc-nd/2.5/deed.en_CA.We report on one aspect of a study that explored the views and experiences of practitioners and scientists on social, ethical and clinical dilemmas encountered when working in the field of preimplantation genetic diagnosis (PGD) for serious genetic disorders. The study produced an ethnography based on observation, interviews and ethics discussion groups with staff from two PGD/IVF Units in the UK. We focus here on staff perceptions of work with embryos that entails disposing of âaffectedâ or âspareâ embryos or using them for research. A variety of views were expressed on the âembryo questionâ in contrast to polarised media debates. We argue that the prevailing policy acceptance of destroying affected embryos, and allowing research on embryos up to 14 days leaves some staff with rarely reported, ambivalent feelings. Staff views are under-researched in this area and we focus on how they may reconcile their personal moral views with the ethical framework in their field. Staff construct embryos in a variety of ways as âmoral work objectsâ. This allows them to shift attention between micro-level and overarching institutional work goals, building on Casper's concept of âwork objectsâ and focusing on negotiation of the social order in a morally contested field.The Wellcome Trust Biomedical Ethics Programme, who funded the projectsâFacilitating choice, framing choice: the experience of staff working in pre-implantation genetic diagnosisâ (no: 074935), and âEthical Frameworks for Embryo Donation:the views and practices of IVF/PGD staffâ (no: 081414)