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DNA repair protein RAD50; hRAD50 (RAD50)
Function:
- component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity & meiosis
- within the MRN complex, RAD50 may be required to bind DNA ends & hold them in close proximity; this could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, & may also stimulate activity of DNA ligases &/or restrict nuclease activity of MRE11A to prevent nucleolytic degradation past a given point
- phosphorylated upon DNA damage, probably by ATM or ATR
- component of the BASC complex
- found in a complex with TERF2
- interacts with RINT1
- interacts with BRCA1 via its N-terminal domain
- interacts with DCLRE1C/Artemis
Cofactor: binds 1 Zn+2 per homodimer (putative)
Structure:
- the Zn+2-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys that coordinate one molecule of Zn+2 with the help of the 2 Cys of the Zn+2-hook of another RAD50 molecule, thereby forming a V-shaped homodimer
- the two heads of the homodimer, which constitute the ATP-binding domain, interact with the MRE11A homodimer
- belongs to the SMC family, RAD50 subfamily
- contains 1 Zn+2-hook domain
Compartment:
- nucleus, telomere
- localizes to discrete nuclear foci after treatment with genotoxic agents
Alternative splicing: named isoforms=3
Expression:
- expressed at very low level in most tissues, except in testis where it is expressed at higher level
- expressed in fibroblasts
General
DNA-binding protein
phosphoprotein
zinc finger protein
Properties
SIZE: entity length = 1312 aa
MW = 154 kD
COMPARTMENT: cell nucleus
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 36-43
coiled coil {228-359}
MOTIF: Ser phosphorylation site {S237}
coiled coil {401-598}
Zinc-hook {635-734}
MOTIF: coiled coil {635-673}
Ser phosphorylation site {S635}
Ser phosphorylation site {S640}
Zn+2-binding site
SITE: 681-681
Zn+2-binding site
SITE: 684-684
Thr phosphorylation site {T690}
coiled coil {706-734}
coiled coil {789-1079}
References
- Khanna KK & Jackson SP
DNA double-strand breaks: signaling, repair and the cancer
connection.
Nature Genetics 27:247-54, 2001
PMID: 11242102
- UniProt :accession Q92878
Component-of
MRN complex
Databases & Figures
OMIM 604040
UniProt Q92878
PFAM correlations
Entrez Gene 10111
Kegg hsa:10111
Figures/diagrams/slides/tables related to DNA repair protein RAD50