DNA mismatch repair in the chromatin context: Mechanisms and therapeutic potential

Yaping Huang; Guo-Min Li

doi:10.1016/j.dnarep.2020.102918

DNA mismatch repair in the chromatin context: Mechanisms and therapeutic potential

DNA Repair (Amst). 2020 Sep:93:102918. doi: 10.1016/j.dnarep.2020.102918.

Authors

Yaping Huang¹, Guo-Min Li²

Affiliations

¹ Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA.
² Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA. Electronic address: guo-min.li@utsouthwestern.edu.

Abstract

DNA mismatch repair (MMR) maintains genomic stability primarily by correcting replication errors. Defects in MMR lead to cancers and cause resistance to many chemotherapeutic drugs. Emerging evidence reveals that MMR is coupled with replication and precisely regulated in the context of chromatin; strikingly, tumors defective in MMR are highly responsive to immune checkpoint blockade therapy. As a tribute to Dr. Samuel Wilson for his many scientific contributions to the field of DNA repair and his leadership as Editor-in-Chief of the journal DNA Repair, we summarize recent developments in research on MMR at the chromatin level, its implications for tumorigenesis, and its therapeutic potential.

Keywords: Cancer therapy; Chromatin structure; Mimsatch repair; Replication fork.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Carcinogenesis
Chromatin / metabolism*
DNA Damage
DNA Mismatch Repair*
Humans
Neoplasms / drug therapy
Neoplasms / genetics

Substances

Chromatin

Grants and funding

R01 GM112702/GM/NIGMS NIH HHS/United States