| 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 |
9.889
|
| Times Cited |
26
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| C.elegans |
tm1354
tm899 |
