The DNA repair helicase RECQ1 has a checkpoint-dependent role in mediating DNA damage responses induced by...

Area of Science:

• Genetics
• Molecular Biology
• Cancer Research

Background:

• DNA repair genes are crucial for cancer drug response.
• RecQ-like helicase 1 (RECQ1) is vital for genome stability.
• RECQ1 loss-of-function mutations link to breast cancer susceptibility.

Purpose of the Study:

• To investigate the role of RECQ1 in breast cancer cell response to gemcitabine.
• To elucidate the mechanisms by which RECQ1 loss affects DNA damage and cell cycle checkpoints.

Main Methods:

• CRISPR/Cas9-edited MDA-MB-231 breast cancer cell model.
• Assessment of cell sensitivity to gemcitabine.
• Analysis of DNA damage accumulation and checkpoint activation (ATR/ChK1).
• Investigated dual deficiency of MUS81 and RECQ1.

Main Results:

• RECQ1 loss sensitized MDA-MB-231 cells to gemcitabine.
• RECQ1 deficiency resulted in defective ATR/ChK1 activation and increased DNA damage.
• Combined MUS81 and RECQ1 deficiency amplified gemcitabine-induced DNA double-strand breaks.
• ChK1 inhibition further sensitized RECQ1-deficient cells to gemcitabine, increasing cell death.

Conclusions:

• RECQ1 plays a significant role in activating cell cycle checkpoints against gemcitabine-induced replication stress.
• Targeting RECQ1 or its associated pathways may enhance gemcitabine efficacy in triple-negative breast cancer.