Mcm10 Interacts with Mrc1 and May Play a Possible Role in DNA Damage Checkpoint Pathway (LB123)

Abstract

To ensure genome integrity, cells must replicate with absolute fidelity. However, cells are constantly under stress that causes DNA damage or block replication. To circumvent these problems, cells have a quality control system termed DNA damage checkpoint. In humans, defects in this checkpoint cause genome instability and a strong predisposition to cancer. A recent study has identified minichromosome maintenance protein 10 (Mcm10) as one of the few replication proteins that prevent DNA damage. However, whether Mcm10 has an active role in preventing DNA damage is unknown. We have observed that Mcm10 and mediator of replication checkpoint 1 (Mrc1) interact in S. cerevisiae whole cell extracts. Moreover, a robust interaction was observed between Mcm10 and Mrc1 by yeast two‐hybrid assays. Our data suggests Mcm10 interacts through the conserved C‐terminus of Mrc1. Interestingly, it is the N‐terminus of Mcm10 that binds to Mrc1. We are currently conducting experiments to further elucidate this interaction. These studies promise to identify a novel role of Mcm10 in DNA damage response pathway and maintenance of genomic integrity. Grant Funding Source: Supported by the National Institute of General Medical Sciences of the National Institutes of Health through Grant Number 8P20GM103447 to SDB.