期刊
DEVELOPMENTAL BIOLOGY
卷 402, 期 2, 页码 253-262出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2015.03.011
关键词
Laboratory mouse; Gametogenesis; Germ cells; Mitosis; Kinesin; Mitotic spindle; Cell cycle
资金
- NICHD [HD078485-01]
- Cancer Center Core Grant [CA34196]
- Basil O'Connor Research Starter Scholar Award [5-FY14-33]
- Vermont Cancer Center/ LCCRO Program Award
Genome integrity in the developing germ line is strictly required for fecundity. In proliferating somatic cells and in germ cells, there are mitotic checkpoint mechanisms that ensure accurate chromosome segregation and euploidy. There is growing evidence of mitotic cell cycle components that are uniquely required in the germ line to ensure genome integrity. We previously showed that the primary phenotype of germ cell deficient 2 (gcd2) mutant mice is infertility due to germ cell depletion during embryogenesis. Here we show that the underlying mutation is a mis-sense mutation, R308K, in the motor domain of the kinesin-8 family member, KIF18A, a protein that is expressed in a variety of proliferative tissues and is a key regulator of chromosome alignment during mitosis. Despite the conservative nature of the mutation, we show that its functional consequences are equivalent to KIF18A deficiency in HeLa cells. We also show that somatic cells progress through mitosis, despite having chromosome alignment defects, while germ cells with similar chromosome alignment defects undergo mitotic arrest and apoptosis. Our data provide evidence for differential requirements for chromosome alignment in germ and somatic cells and show that Kif18a is one of a growing number of genes that are specifically required for cell cycle progression in proliferating germ cells. (C) 2015 Elsevier Inc. All rights reserved.
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