The MRT-1 nuclease is required for DNA crosslink repair and telomerase activity in vivo in Caenorhabditis elegans

Bettina Meier, Louise J. Barber, Yan Liu, Ludmila Shtessel, Simon J. Boulton, Anton Gartner, Shawn Ahmed

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    The telomerase reverse transcriptase adds de novo DNA repeats to chromosome termini. Here we define Caenorhabditis elegans MRT-1 as a novel factor required for telomerase-mediated telomere replication and the DNA-damage response. MRT-1 is composed of an N-terminal domain homologous to the second OB-fold of POT1 telomere-binding proteins and a C-terminal SNM1 family nuclease domain, which confer single-strand DNA-binding and processive 3'-to-5' exonuclease activity, respectively. Furthermore, telomerase activity in vivo depends on a functional MRT-1 OB-fold. We show that MRT-1 acts in the same telomere replication pathway as telomerase and the 9-1-1 DNA-damage response complex. MRT-1 is dispensable for DNA double-strand break repair, but functions with the 9-1-1 complex to promote DNA interstrand cross-link (ICL) repair. Our data reveal MRT-1 as a dual-domain protein required for telomerase function and ICL repair, which raises the possibility that telomeres and ICL lesions may share a common feature that plays a critical role in de novo telomere repeat addition. The EMBO Journal (2009) 28, 3549-3563. doi:10.1038/emboj.2009.278; Published online 24 September 2009

    Original languageEnglish
    Pages (from-to)3549-3563
    Number of pages15
    JournalEMBO Journal
    Volume28
    Issue number22
    DOIs
    Publication statusPublished - 18 Nov 2009

    Keywords

    • C. elegans
    • ICL
    • POT1
    • SNM1
    • telomerase
    • METALLO-BETA-LACTAMASE
    • END-BINDING-PROTEIN
    • DAMAGE CHECKPOINT PROTEIN
    • SINGLE-STRANDED-DNA
    • GENOME-WIDE SCREEN
    • SACCHAROMYCES-CEREVISIAE
    • TETRAHYMENA TELOMERASE
    • C-ELEGANS
    • REVERSE-TRANSCRIPTASE
    • FISSION YEAST

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