APE1-dependent base excision repair of DNA photodimers in human cells.

Abstract

UV irradiation induces "bulky" DNA photodimers such as (6-4)-photoproducts and cyclobutane pyrimidine dimers that are removed by nucleotide excision repair, a complex process defective in the sunlight-sensitive and cancer-prone disease xeroderma pigmentosum. Some bacteria and lower eukaryotes can also repair photodimers by enzymatically simpler mechanisms, but such pathways have not been reported in normal human cells. Here, we have identified such a mechanism. We show that normal human cells can employ a DNA base excision repair process involving NTH1, APE1, PARP1, XRCC1, and FEN1 to rapidly remove a subset of photodimers at early times following UVC irradiation. Loss of these proteins slows the early rate of repair of photodimers in normal cells, ablates their residual repair in xeroderma pigmentosum cells, and increases UVC sensitivity ∼2-fold. These data reveal that human cells can excise photodimers using a long-patch base excision repair process that functions additively but independently of nucleotide excision repair.

• Authors: Amit Gautam, Heather Fawcett, Kamila Burdova, Jan Brazina, Keith W Caldecott
• Journal: Molecular cell (Mol Cell) Vol. 83 Issue 20 Pg. 3669-3678.e7 (10 19 2023) ISSN: 1097-4164 [Electronic] United States
• PMID: 37816354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Pyrimidine Dimers
• DNA
• XRCC1 protein, human
• X-ray Repair Cross Complementing Protein 1

Topics

• Humans
• Xeroderma Pigmentosum (genetics)
• DNA Repair (genetics)
• Pyrimidine Dimers (genetics, metabolism)
• DNA Damage (genetics)
• DNA (genetics)
• Ultraviolet Rays
• X-ray Repair Cross Complementing Protein 1 (metabolism)