A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13

被引:55
作者
Johnson, EM
Kinoshita, Y
Daniel, DC
机构
[1] CUNY Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA
[2] CUNY Mt Sinai Sch Med, Dept Mol Biol, New York, NY 10029 USA
[3] CUNY Mt Sinai Sch Med, DH Ruttenberg Canc Ctr, New York, NY 10029 USA
关键词
D O I
10.1093/nar/gkg395
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2915 / 2925
页数:11
相关论文
共 35 条
[31]   IDENTIFICATION OF 2 INITIATOR ELEMENTS IN THE BIDIRECTIONAL PROMOTER OF THE HUMAN DIHYDROFOLATE-REDUCTASE AND MISMATCH REPAIR PROTEIN-1 GENES [J].
SHINYA, E ;
SHIMADA, T .
NUCLEIC ACIDS RESEARCH, 1994, 22 (11) :2143-2149
[32]   MCM proteins in DNA replication [J].
Tye, BK .
ANNUAL REVIEW OF BIOCHEMISTRY, 1999, 68 :649-686
[33]   DISTANTLY RELATED SEQUENCES IN THE ALPHA-SUBUNITS AND BETA-SUBUNITS OF ATP SYNTHASE, MYOSIN, KINASES AND OTHER ATP-REQUIRING ENZYMES AND A COMMON NUCLEOTIDE BINDING FOLD [J].
WALKER, JE ;
SARASTE, M ;
RUNSWICK, MJ ;
GAY, NJ .
EMBO JOURNAL, 1982, 1 (08) :945-951
[34]   NBR1 interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB) and shows developmentally restricted expression in the neural tube [J].
Whitehouse, C ;
Chambers, J ;
Howe, K ;
Cobourne, M ;
Sharpe, P ;
Solomon, E .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2002, 269 (02) :538-545
[35]  
You ZY, 1999, MOL CELL BIOL, V19, P8003