Identification and characterization of a paralog of human cell cycle checkpoint gene HUS1.
A paralog of the human cell cycle checkpoint gene HUS1 has been identified and designated HUS1B. It encodes a 278-amino-acid protein, 48% identical and 69% similar to HUS1. Mouse and rat orthologs of HUS1B have also been detected by a BLAST search. HUS1B is expressed variably in many human tissues, and the tissue-specific levels observed parallel those for HUS1. A HUS1-RAD1-RAD9 protein complex is thought to form a proliferating cell nuclear antigen (PCNA)-like structure, important for cell cycle checkpoint function. However, HUS1B directly interacts with RAD1, but not RAD9 or HUS1, whereas HUS1 can bind RAD1, RAD9, and another molecule of HUS1, suggesting that HUS1B cannot simply substitute for HUS1 in the complex. HUS1B is less conserved evolutionarily than HUS1. Furthermore, overexpression of HUS1B but not HUS1 in human cells induces clonogenic cell death. We suggest that HUS1B and HUS1 have distinct but related roles in regulating cell cycle checkpoints and genomic integrity.
Hang
Haiying
H
Center for Radiological Research, Columbia University, 630 West 168th Street, New York, New York 10032, USA. hh91@columbia.edu
Zhang
Yuzhu
Y
Dunbrack
Roland L
RL
Wang
Cuidong
C
Lieberman
Howard B
HB
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D018816:Genes, cdc; D015894:Genome, Human; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; C549605:HUS1 protein, human; C462949:HUS1B protein, human; D029702:Schizosaccharomyces pombe Proteins; C106332:hus1 protein, S pombe