A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13.
The MCM8 protein from HeLa cells, a new member of the MCM family, co-isolates through several steps with MCM6 and MCM7, and MCM8 co-immunoprecipitates with MCM4, MCM6 and MCM7, proteins reportedly forming a helicase complex involved in initiation of DNA replication. MCM8 mRNA is expressed in placenta, lung and liver, but is also significantly expressed in adult heart, a tissue with a low percentage of proliferating cells. The MCM8 gene, consisting of 19 exons, is located contrapodal to a gene, consisting of 11 exons, encoding a homolog of the yeast GCD10 gene product. The region between these two transcription units, comprising as few as 62 bp, is TATA-less and highly GC-rich, containing multiple CpG units. MCM8 expression is altered in certain forms of neoplasia. In a case of choriocarcinoma MCM8 mRNA is aberrant, leading to expression of a protein lacking 16 amino acids. In several cases of colon adenocarcinoma MCM8 expression is greatly reduced relative to matched non-cancerous tissue. The potential helicase domain of MCM8 is different from those of other MCM proteins in that it is more homologous to canonical ATP-binding domains of other known helicases. Results suggest that MCM8 may interact with other MCM proteins to alter the function of the replicative MCM protein complex.
Johnson
Edward M
EM
Department of Pathology, Box 1194, Mount Sinai School of Medicine, New York, NY 10029, USA.
Kinoshita
Yayoi
Y
Daniel
Dianne C
DC
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism; D002890:Chromosomes, Human, Pair 20; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D004261:DNA Replication; D040461:Gene Components; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D064110:Minichromosome Maintenance Proteins; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D016415:Sequence Alignment; D014018:Tissue Distribution
C475077:CRLS1 protein, human; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D004265:DNA Helicases; C471623:MCM8 protein, human; D064110:Minichromosome Maintenance Proteins