Deletion of INMAP postpones mitotic exit and induces apoptosis by disabling the formation of mitotic spindle

Area of Science:

• Cell Biology
• Genetics
• Molecular Biology

Background:

• INMAP is a spindle protein crucial for cell-cycle progression.
• Abnormal INMAP expression is linked to mitotic disorders and tumor growth inhibition, but mechanisms remain unclear.

Purpose of the Study:

• To investigate the role of INMAP in maintaining genomic stability and cell cycle progression.
• To elucidate the underlying mechanisms of INMAP's function in human embryonic renal cells.

Main Methods:

• CRISPR-Cas9 gene editing was used to knock out INMAP in HEK293T cells.
• Cell growth, apoptosis, DNA damage markers (micronuclei, chromosome aberrations, γH2AX), and cell cycle proteins (β-tubulin, Cyclin B, Cyclin E) were analyzed.

Main Results:

• INMAP knockout led to significant cell growth inhibition, increased apoptosis, and DNA damage.
• Micronuclei formation, chromosome aberrations, and γH2AX upregulation indicated impaired genomic stability.
• Absence of INMAP resulted in β-tubulin and Cyclin B upregulation, Cyclin E downregulation, delayed mitotic exit, and spindle assembly defects.

Conclusions:

• INMAP deletion disrupts spindle formation, leading to cell cycle arrest and DNA damage.
• INMAP is indispensable for maintaining genomic integrity and ensuring normal mitotic exit.
• These findings identify INMAP as a critical factor in preventing mitotic disorders and maintaining cellular homeostasis.