Role of the BLM helicase in replication fork management.

Cancer Research UK, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom.
DNA Repair (Impact Factor: 3.36). 08/2007; 6(7):936-44. DOI: 10.1016/j.dnarep.2007.02.007
Source: PubMed

ABSTRACT Genomic DNA is particularly vulnerable to mutation during S-phase when the two strands of parental duplex DNA are separated during the process of semi-conservative DNA replication. Lesions that are normally repaired efficiently in the context of double stranded DNA can cause replication forks to stall or, more dangerously, collapse. Cells from Bloom's syndrome patients, that lack the RecQ helicase BLM, show defects in the response to replicative stress and contain a multitude of chromosomal aberrations, which primarily arise through excessive levels of homologous recombination. Here, recent findings are reviewed that further our understanding of the role that BLM plays in the management of damaged replication forks.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Strand-seq is a single-cell sequencing technique to finely map sister chromatid exchanges (SCEs) and other rearrangements. To analyze these data, we introduce BAIT software, which assigns templates and identifies and localizes SCEs. We demonstrate BAIT can refine completed reference assemblies, identifying approximately 21 Mb of incorrectly-oriented fragments and placing over half (2.6 Mb) of the orphan fragments in mm10/GRCm38. BAIT also stratifies scaffold-stage assemblies, potentially accelerating the assembling and finishing of reference genomes. BAIT is available at
    Genome Medicine 09/2013; 5(9):82. DOI:10.1186/gm486 · 4.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The approach to traditional teaching methods and student assessment leads to passivity. When learning is passive, can not make connections between what is taught and what the student knows, he must explain to the others. The mosaic is an interactive method of teaching physics. Carefully prepared, this method will be very appreciated by the high school students and will stimulate an academic approach. Basically, each student works (specialize) in a sequence, but the rest receives from colleagues. This article offers a version of mosaic method (Jigsaw method) for enhancing knowledge of atomic physics.
    Procedia - Social and Behavioral Sciences 01/2011; 15:1605-1610. DOI:10.1016/j.sbspro.2011.03.338
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Mammalian BLM helicase is involved in DNA replication, DNA repair and homologous recombination (HR). These DNA transactions are associated tightly with cell division and are important for maintaining genome stability. However, unlike in mammals, cell division in higher plants is restricted mainly to the meristem, thus genome maintenance at the meristem is critical. The counterpart of BLM in Arabidopsis (AtRecQ4A) has been identified and its role in HR and in the response to DNA damage has been confirmed. However, the function of AtRecQ4A in the meristem during replication stress has not yet been well elucidated. Results We isolated the BLM counterpart gene OsRecQl4 from rice and analyzed its function using a reverse genetics approach. Osrecql4 mutant plants showed hypersensitivity to DNA damaging agents and enhanced frequency of HR compared to wild-type (WT) plants. We further analyzed the effect of aphidicolin—an inhibitor of S-phase progression via its inhibitory effect on DNA polymerases—on genome stability in the root meristem in osrecql4 mutant plants and corresponding WT plants. The following effects were observed upon aphidicolin treatment: a) comet assay showed induction of DNA double-strand breaks (DSBs) in mutant plants, b) TUNEL assay showed enhanced DNA breaks at the root meristem in mutant plants, c) a recombination reporter showed enhanced HR frequency in mutant calli, d) propidium iodide (PI) staining of root tips revealed an increased incidence of cell death in the meristem of mutant plants. Conclusions These results demonstrate that the aphidicolin-sensitive phenotype of osrecql4 mutants was in part due to induced DSBs and cell death, and that OsRecQl4 plays an important role as a caretaker, maintaining genome stability during DNA replication stress in the rice meristem.
    BMC Plant Biology 04/2013; 13(1):62. DOI:10.1186/1471-2229-13-62 · 3.94 Impact Factor