Defective Inhibition of DNA Recombination at Telomere

Stable Identifier
R-HSA-9670621
Type
Pathway
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Defective Inhibition of DNA Recombination at Telomere
Click the image above or here to open this pathway in the Pathway Browser
ATRX (Alpha thalassemia mental retardation X-lined) and DAXX (Death domain-associated protein 6) chromatin remodeling factors form a complex that binds to subtelomeric regions and plays a role in inhibition of DNA recombination at telomere ends, probably by mediating loading of H3F3A histone at telomere ends and by repressing transcription of TERRA (Telomeric repeat containing RNA), a long noncoding telomeric repeats-containing RNA. Tumors positive for alternative lengthening of telomeres (ALT) markers often harbor loss-of-function mutations in ATRX, and more rarely in DAXX or missense mutations in H3F3A, implying that the impairment of function of one of these three proteins may contribute to initiation of the ALT process. Additionally, mutations in IDH, the tumor suppressor TP53 and SMARCAL1 are also observed in the context of ALT in certain types of human cancers, particularly sarcomas and tumors of the central nervous system (Jiao et al. 2012, Nicolle et al. 2019). For review, please refer to Gocha et al. 2013, Pickett and Reddel 2015, Amorim et al. 2016).
Literature References
PubMed ID Title Journal Year
27657132 The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype

Santos, G, Soares, P, Vinagre, J, Amorim, JP

Genes (Basel) 2016
22869205 Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas

Lipp, E, He, Y, Pirozzi, C, Diaz, LA, Nagahashi Marie, SK, Rodriguez, FJ, Holdhoff, M, Oba-Shinjo, SM, Papadopoulos, N, McLendon, R, Bettegowda, C, Reitman, ZJ, Kinzler, KW, Vogelstein, B, Agrawal, N, Rasheed, AB, Yan, H, Friedman, AH, Riggins, GJ, Friedman, H, Meeker, AK, Killela, PJ, Lopez, G, Burger, P, Jiao, Y, de Wilde, RF, Bigner, DD, Heaphy, CM, Rosemberg, S

Oncotarget 2012
31604924 Integrated molecular characterization of chondrosarcoma reveals critical determinants of disease progression

Anract, P, Decouvelaere, AV, Marie, B, Larousserie, F, Karanian, M, le Nail, LR, Rédini, F, Armenoult, L, de Reyniès, A, Ayadi, M, Aubert, S, Gomez-Brouchet, A, Reina, N, Tallegas, M, Banneau, G, Labit-Bouvier, C, Gouin, F, de Pinieux, G, Elarouci, N, Nicolle, R

Nat Commun 2019
23219603 Alternative mechanisms of telomere lengthening: permissive mutations, DNA repair proteins and tumorigenic progression

Groden, J, Gocha, AR, Harris, J

Mutat. Res. 2013
26581522 Molecular mechanisms of activity and derepression of alternative lengthening of telomeres

Reddel, RR, Pickett, HA

Nat. Struct. Mol. Biol. 2015
Participants
Events
Participates
as an event of
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M  (2020-04-30)
Reviewed
Reddel, RR  (2020-11-13)
Meeker, AK  (2020-11-05)
Created
Orlic-Milacic, M  (2019-12-11)
Cite Us!