InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DCLRE1B

Summary

InnateDB Protein

IDBP-101256.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DCLRE1B

Protein Name

DNA cross-link repair 1B

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000358576

InnateDB Gene

IDBG-101254 (DCLRE1B)

Protein Structure

UniProt Annotation

Function

5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)- mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways. Together with TERF2, required to protect telomeres from replicative damage during replication by controlling the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Also involved in response to DNA damage: plays a role in response to DNA interstrand cross-links (ICLs) by facilitating double-strand break formation. In case of spindle stress, involved in prophase checkpoint. {ECO:0000269PubMed:15467758, ECO:0000269PubMed:15572677, ECO:0000269PubMed:16730175, ECO:0000269PubMed:16730176, ECO:0000269PubMed:18468965, ECO:0000269PubMed:18469862, ECO:0000269PubMed:19197158, ECO:0000269PubMed:19411856, ECO:0000269PubMed:20655466}.

Subcellular Localization

Chromosome, telomere. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Mainly localizes to telomeres, recruited via its interaction with TERF2. During mitosis, localizes to the centrosome.

Disease Associations

Hoyeraal-Hreidarsson syndrome (HHS) [MIM:305000]: A clinically severe variant of dyskeratosis congenita that is characterized by multisystem involvement, early onset in utero, and often results in death in childhood. Affected individuals show intrauterine growth retardation, microcephaly, cerebellar hypoplasia, delayed development, and bone marrow failure resulting in immunodeficiency. {ECO:0000269PubMed:20479256}. Note=The gene represented in this entry may be involved in disease pathogenesis. An aberrant splice variant of DCLRE1B, designated Apollo-Delta, has been found in a patient with Hoyeraal-Hreidarsson syndrome (PubMed:20479256). Apollo-Delta hampers the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence, but maintains its DNA interstrand cross-link repair function in the whole genome. {ECO:0000269PubMed:20479256}.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.

Experimentally validated
Total	11 [view]
Protein-Protein	9 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008409	5'-3' exonuclease activity

Biological Process

GO:0000075	cell cycle checkpoint
GO:0000723	telomere maintenance
GO:0006281	DNA repair
GO:0031627	telomeric loop formation
GO:0031848	protection from non-homologous end joining at telomere
GO:0031860	telomeric 3' overhang formation
GO:0090305	nucleic acid phosphodiester bond hydrolysis