RRC ID 6404
Author Meier B, Barber LJ, Liu Y, Shtessel L, Boulton SJ, Gartner A, Ahmed S.
Title The MRT-1 nuclease is required for DNA crosslink repair and telomerase activity in vivo in Caenorhabditis elegans.
Journal EMBO J.
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.
Volume 28(22)
Pages 3549-63
Published 2009-11-18
DOI 10.1038/emboj.2009.278
PII emboj2009278
PMID 19779462
PMC PMC2782091
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* DNA Damage / physiology DNA Repair / genetics* DNA, Single-Stranded / metabolism Deoxyribonucleases / chemistry Deoxyribonucleases / genetics Deoxyribonucleases / metabolism Deoxyribonucleases / physiology* Enzyme Activation / genetics Molecular Sequence Data Protein Binding Protein Structure, Tertiary / genetics Sequence Homology, Amino Acid Telomerase / metabolism* Telomere / metabolism
IF 10.557
Times Cited 18
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
C.elegans tm1354 tm899