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FLASH GENE

Symbol

RAD50

contributors: mct/pgu - updated : 31-01-2013

HGNC name	RAD50 homolog (S. cerevisiae)
HGNC id	9816

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	NBSLD Nijmegen breakage syndrome -like disorder
Location	5q31.1      Physical location : 131.892.615 - 131.980.312
Synonym symbol(s)	MRE11, RAD50-2, hRad50, NBSLD, RAD502

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
text	clustered with KIF3A, IL13 and IL4
STRUCTURE	87.70 kb     24 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

regionally located

in a locus control region regulating T helper 2 -specific expression of IL4 and IL13

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005732 24 - 6597 NP_005723 153.7 1312 - 1999 10415333 RAD50-1 larger 3'utr than RAD50.2 RAD50.3 25 - 5826 138.3 1173 ubiquitous 1999 10415333 lacking the ATP binding domain

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth       highly Endocrine pancreas         Reproductive male system testis       Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Epithelial secretory glandular exocrine

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	SMC N-terminal ATP binding domain
	central heptad repeat domain
	zinc hook domain mediating zinc-dependent intercomplex associations of MRN (MRE11-RAD50-NBS1), which is important for DNA tethering

HOMOLOGY

interspecies

homolog to yeast S.cerevisiae RAD50

Homologene

FAMILY

CATEGORY

DNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome,telomere

basic FUNCTION	involved in DNA double-strand break repair by end joining (non homologous recombination) and meiosis specific double strand break formation
	essential for cell growth and viability
	having a biological role as an early participant in cellular DNA-damage responses
	role of MRN in the maintenance of genome stability through preventing rereplication and rereplication-associated double-stranded breaks when licensing control is compromised
	MRE11A/RAD50/NBS1 (MRN) complex has a central function in facilitating activation of the ATM protein kinase at sites of DNA double-strand breaks (DSBs)
	phosphorylation of RAD50 plays a key regulatory role as an adaptor for specific ATM-dependent downstream signaling through SMC1 for DNA repair and cell cycle checkpoint control in the maintenance of genome integrity
	functions of MRE11 complex are integrated by the coiled coils of RAD50
	ATP hydrolysis opens the RAD50-MRE11A complex, and MRE11A maintains exonuclease activity

CELLULAR PROCESS	nucleotide, repair, recombination
	nucleotide, genomic integrity

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	complexing with MRE11A and NBN, exonuclease 3' to 5' and endonuclease activities and with BLM (complex MRE11A, RAD50 and NBN (MRN), are central to maintaining genomic stability)
	MR complex contains the MRE11A nuclease dimer and two flanking RAD50 ATPase domains

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	BLM, WRN, MRE11A, NBN
	interaction with RAD50, XRS2/NBN, complex required for TERF1 phosphorylation by ATM and such phosphorylation results in the release of TERF1 from telomeres, promoting telomerase access to the ends of telomeres
	interacting with NBN in a stable complex, in absence of MRE11
	NCL interacts with RAD50 via its arginine-glycine rich domain and is recruited to DSBs rapidly in an MRE11-NBS1-RAD50 complex-dependent manner
	BRCA1 and BLM interact with RAD50 predominantly in S- and G2-phases, respectively

cell & other

REGULATION

Phosphorylated by

ATM, that phosphorylates RAD50 at a single site (Ser-635) that plays an important adaptor role in signaling for cell cycle control and DNA repair

ASSOCIATED DISORDERS

corresponding disease(s)

NBSLD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in microsatellite stable (MSS) colorectal cancers tumoral germinal mutation     loss of function in patients with primary ovarian, fallopian tube, or peritoneal cancers tumoral     --over   in melanoma cells

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS