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The MRT‐1 nuclease is required for DNA crosslink repair and telomerase activity in vivo in Caenorhabditis elegans
Author(s) -
Meier Bettina,
Barber Louise J,
Liu Yan,
Shtessel Ludmila,
Boulton Simon J,
Gartner Anton,
Ahmed Shawn
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.278
Subject(s) - biology , caenorhabditis elegans , nuclease , telomerase , in vivo , microbiology and biotechnology , dna , dna damage , genetics , dna repair , gene
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.