The DNA polymerase λ is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells

DNA polymerase lambda (polλ) is a recently identified DNA polymerase whose cellular function remains elusive. Here we show, that polλ participates at the molecular level in a chromosomal context, in the repair of DNA double strand breaks (DSB) via non-homologous end joining (NHEJ) in mammalian cells. The expression of a catalytically inactive form of polλ (polλDN) decreases the frequency of NHEJ events in response to I-Sce-I-induced DSB whereas inactivated forms of its homologues polβ and polμ do not. Only events requiring DNA end processing before ligation are affected; this defect is associated with large deletions arising in the vicinity of the induced DSB. Furthermore, polλDN-expressing cells exhibit increased sensitization and genomic instability in response to ionizing radiation similar to that of NHEJ-defective cells. Our data support a requirement for polλ in repairing a subset of DSB in genomic DNA, thereby contributing to the maintenance of genetic stability mediated by the NHEJ pathway

Detection in coincidence of gravitational wave bursts with a network of interferometric detectors (I): Geometric acceptance and timing

Detecting gravitational wave bursts (characterised by short durations and poorly modelled waveforms) requires to have coincidences between several interferometric detectors in order to reject non-stationary noise events. As the wave amplitude seen in a detector depends on its location with respect to the source direction and as the signal to noise ratio of these bursts are expected to be low, coincidences between antennas may not be so likely. This paper investigates this question from a statistical point of view by using a simple model of a network of detectors; it also estimates the timing precision of a detection in an interferometer which is an important issue for the reconstruction of the source location, based on time delays.Comment: low resolution figure 1 due to file size problem

DETECTION DES ONDES GRAVITATIONNELLES EMISES PAR DES ETOILES BINAIRES COMPACTES SPIRALANTES AVEC L'INTERFEROMETRE VIRGO

ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

JMJD6 participates in the maintenance of ribosomal DNA integrity in response to DNA damage.

Ribosomal DNA (rDNA) is the most transcribed genomic region and contains hundreds of tandem repeats. Maintaining these rDNA repeats as well as the level of rDNA transcription is essential for cellular homeostasis. DNA damages generated in rDNA need to be efficiently and accurately repaired and rDNA repeats instability has been reported in cancer, aging and neurological diseases. Here, we describe that the histone demethylase JMJD6 is rapidly recruited to nucleolar DNA damage and is crucial for the relocalisation of rDNA in nucleolar caps. Yet, JMJD6 is dispensable for rDNA transcription inhibition. Mass spectrometry analysis revealed that JMJD6 interacts with the nucleolar protein Treacle and modulates its interaction with NBS1. Moreover, cells deficient for JMJD6 show increased sensitivity to nucleolar DNA damage as well as loss and rearrangements of rDNA repeats upon irradiation. Altogether our data reveal that rDNA transcription inhibition is uncoupled from rDNA relocalisation into nucleolar caps and that JMJD6 is required for rDNA stability through its role in nucleolar caps formation

Senataxin resolves RNA:DNA hybrids forming at DNA double-strand breaks to prevent translocations

International audienceAtaxia with oculomotor apraxia 2 (AOA-2) and amyotrophic lateral sclerosis (ALS4) are neurological disorders caused by mutations in the gene encoding for senataxin (SETX), a putative RNA:DNA helicase involved in transcription and in the maintenance of genome integrity. Here, using ChIP followed by high throughput sequencing (ChIP-seq), we report that senataxin is recruited at DNA double-strand breaks (DSBs) when they occur in transcriptionally active loci. Genome-wide mapping unveiled that RNA:DNA hybrids accumulate on DSB-flanking chromatin but display a narrow, DSB-induced, depletion near DNA ends coinciding with senataxin binding. Although neither required for resection nor for timely repair of DSBs, senataxin was found to promote Rad51 recruitment, to minimize illegitimate rejoining of distant DNA ends and to sustain cell viability following DSB production in active genes. Our data suggest that senataxin functions at DSBs in order to limit translocations and ensure cell viability, providing new insights on AOA2/ALS4 neuropathies

Effect of the expression of the polβ and polμ inactive form on NHEJ events

<p><b>Copyright information:</b></p><p>Taken from "The DNA polymerase λ is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells"</p><p>Nucleic Acids Research 2006;34(10):2998-3007.</p><p>Published online 31 May 2006</p><p>PMCID:PMC1474058.</p><p>© 2006 The Author(s)</p> ( and ) Representation of the sequences of the I-Sce-I restriction sites in the C′10 and A′7H cell lines, respectively. In the C′10 cells the two I-Sce-I sites are in direct orientation whereas in the A′7H cells the two I-Sce-I sites are in inverted orientation (upper panel). Evaluation of the frequency of the deletion (CD4) and inversion (CD8) events in the different cell lines (median panel). Results are the mean +/− SD of three independent experiments. Western blots for polβ and polμ expression in the different cell lines (lower panel)