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RAD1 CHECKPOINT DNA EXONUCLEASE; RAD1

RAD1 CHECKPOINT DNA EXONUCLEASE; RAD1

Alternative titles; symbolsRAD1, S. POMBE, HOMOLOG OFHGNC Approved Gene Symbol: RAD1Cytogenetic location: 5p13.2 Genomic coordinates (GRCh38): 5:34,905,259-3...

Alternative titles; symbols

  • RAD1, S. POMBE, HOMOLOG OF

HGNC Approved Gene Symbol: RAD1

Cytogenetic location: 5p13.2 Genomic coordinates (GRCh38): 5:34,905,259-34,915,503 (from NCBI)

▼ Cloning and Expression
In the fission yeast S. pombe, the rad1+ gene product is required for DNA repair and replication. Parker et al. (1998) cloned 2 alternatively spliced human cDNAs encoding proteins with significant homology to yeast rad1+. The longer cDNA, called Hrad1A, encodes a 282-amino acid polypeptide, while Hrad1B encodes a 163-amino acid polypeptide. Northern blot analysis revealed that human RAD1 is expressed as mRNAs of 5, 3, and 1.3 kb in a variety of human tissues, with higher levels present in some cancer cell lines. Northern blot analysis of cells subjected to ultraviolet radiation demonstrated that human RAD1 expression is not induced in response to DNA damage. Purified RAD1 exhibited terminal exonuclease activity on double-stranded DNA, with a preference for 3-prime ends.

Independently, Udell et al. (1998) isolated RAD1 cDNAs from a spontaneously transformed human keratinocyte cDNA library. The cDNAs encode the 282-amino acid RAD1 isoform, which is 90% and 27% identical to mouse Rad1 and S. pombe rad1+, respectively. Udell et al. (1998) found that expression of human RAD1 in yeast rad1 mutants partially restores radiation resistance and G2 checkpoint proficiency.

▼ Gene Function
Volkmer and Karnitz (1999) demonstrated that the human RAD1 and HUS1 (603760) proteins associate in a complex that interacts with a highly modified form of RAD9 (603761). They concluded that these 3 proteins are central components of a DNA damage-responsive protein complex in human cells.

▼ Mapping
Parker et al. (1998) used fluorescence in situ hybridization to map the RAD1 gene to human chromosome 5p13.3-p13.2. The authors stated that loss of heterozygosity (LOH) of this region has been linked to a variety of human neoplasias. This mapping assignment was confirmed by Dean et al. (1998) using fluorescence in situ hybridization and radiation hybrid analysis.

Tags: 5p13.2