MCM8 interacts with DDX5 to promote R-loop resolution

Area of Science:

• Genetics
• Reproductive Biology
• Genomic Stability

Background:

• MCM8 is a key gene in reproductive aging and meiotic repair.
• Its role in mitotic germ cells and genome stability was previously unclear.

Purpose of the Study:

• To investigate the function of MCM8 in mitotic germ cells.
• To understand MCM8's role in maintaining genome integrity and reproductive health.

Main Methods:

• Disabling MCM8 gene in mice.
• Analyzing primordial germ cell (PGC) proliferation and fertility.
• Investigating MCM8's interaction with helicases DDX5 and DHX9.
• Assessing R-loop accumulation and DNA damage.

Main Results:

• MCM8 deficiency caused PGC proliferation defects and infertility in mice.
• MCM8 loss led to R-loop accumulation by reducing DDX5 and DHX9 helicase retention.
• Mutant MCM8 with reduced DDX5 interaction showed increased R-loop levels.
• This induced genome instability in germ cells.

Conclusions:

• MCM8 interacts with R-loop resolving factors to prevent DNA damage.
• MCM8 is essential for PGC development and maintaining genome integrity.
• This study enhances understanding of MCM8's role in reproductive aging and germ cell genome stability.