TY - JOUR
T1 - Formation and repair of DNA-protein crosslink damage
AU - Klages-Mundt, Naeh L.
AU - Li, Lei
N1 - Funding Information:
Acknowledgements We thank Erica Lynn for helpful comments on the manuscript. This work was supported by the National Institutes of Health (CA179441, CA193124-Project 3 to Lei Li) and the Olive Stringer Endowed Professorship (Lei Li).
Publisher Copyright:
© 2017, Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - DNA is constantly exposed to a wide array of genotoxic agents, generating a variety of forms of DNA damage. DNA-protein crosslinks (DPCs)—the covalent linkage of proteins with a DNA strand—are one of the most deleterious and understudied forms of DNA damage, posing as steric blockades to transcription and replication. If not properly repaired, these lesions can lead to mutations, genomic instability, and cell death. DPCs can be induced endogenously or through environmental carcinogens and chemotherapeutic agents. Endogenously, DPCs are commonly derived through reactions with aldehydes, as well as through trapping of various enzymatic intermediates onto the DNA. Proteolytic cleavage of the protein moiety of a DPC is a general strategy for removing the lesion. This can be accomplished through a DPC-specific protease and and/or proteasome-mediated degradation. Nucleotide excision repair and homologous recombination are each involved in repairing DPCs, with their respective roles likely dependent on the nature and size of the adduct. The Fanconi anemia pathway may also have a role in processing DPC repair intermediates. In this review, we discuss how these lesions are formed, strategies and mechanisms for their removal, and diseases associated with defective DPC repair.
AB - DNA is constantly exposed to a wide array of genotoxic agents, generating a variety of forms of DNA damage. DNA-protein crosslinks (DPCs)—the covalent linkage of proteins with a DNA strand—are one of the most deleterious and understudied forms of DNA damage, posing as steric blockades to transcription and replication. If not properly repaired, these lesions can lead to mutations, genomic instability, and cell death. DPCs can be induced endogenously or through environmental carcinogens and chemotherapeutic agents. Endogenously, DPCs are commonly derived through reactions with aldehydes, as well as through trapping of various enzymatic intermediates onto the DNA. Proteolytic cleavage of the protein moiety of a DPC is a general strategy for removing the lesion. This can be accomplished through a DPC-specific protease and and/or proteasome-mediated degradation. Nucleotide excision repair and homologous recombination are each involved in repairing DPCs, with their respective roles likely dependent on the nature and size of the adduct. The Fanconi anemia pathway may also have a role in processing DPC repair intermediates. In this review, we discuss how these lesions are formed, strategies and mechanisms for their removal, and diseases associated with defective DPC repair.
KW - DNA-protein crosslinks
KW - Fanconi anemia
KW - SPRTN
KW - nucleotide excision repair
UR - http://www.scopus.com/inward/record.url?scp=85032967438&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032967438&partnerID=8YFLogxK
U2 - 10.1007/s11427-017-9183-4
DO - 10.1007/s11427-017-9183-4
M3 - Review article
C2 - 29098631
AN - SCOPUS:85032967438
SN - 1674-7305
VL - 60
SP - 1065
EP - 1076
JO - Science China Life Sciences
JF - Science China Life Sciences
IS - 10
ER -