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Psoralen-mediated DNA crosslinking

Molecular classification
Other (DNA adduct/chemical modification)
01

Overview

Psoralens are a class of naturally occurring compounds known as furocoumarins that can intercalate into double-stranded nucleic acids such as DNA. Upon exposure to ultraviolet A (UVA) light, psoralens undergo a [2+2] photocycloaddition reaction with the C5–C6 double bonds of pyrimidine bases—primarily thymine and cytosine—resulting in the formation of covalent interstrand or intrastrand crosslinks within the nucleic acid[3][4]. This chemical modification disrupts normal base pairing and blocks essential processes such as replication and transcription. In biological systems, extensive psoralen-mediated DNA crosslinking is highly cytotoxic. The inability to repair these lesions can trigger cell cycle arrest and ultimately lead to apoptosis. This mechanism underlies the clinical application of psoralens in photochemotherapy (PUVA), where they are used to induce targeted cell death—for example, in certain skin disorders or cutaneous T-cell lymphoma. However, "Lymphocyte apoptosis via psoralen-mediated DNA crosslinking" is not itself a canonical molecular target like an enzyme or receptor; rather, it describes a process whereby lymphocytes undergo programmed cell death due to chemically induced genomic damage. The actual molecular targets are the pyrimidine bases within cellular DNA that react with activated psoralens[3]. Therefore, this entry does not correspond to a specific protein or receptor but rather refers broadly to chemically induced cellular events resulting from targeted nucleic acid modification. If you require structured information on an actual protein target involved in lymphocyte apoptosis pathways (such as Fas receptor/CD95), please specify further.

Other names
Psoralen-DNA crosslinkingPsoralen-induced DNA interstrand crosslinksFurocoumarin-DNA adducts
02

Mechanism of action

Intercalation of psoralen into double-stranded DNA followed by UV-induced [2+2] photocycloaddition to form covalent interstrand crosslinks between pyrimidine bases[3][4]

03

Biological functions

DNA damageApoptosis (indirectly, as a consequence of DNA damage)
04

Disease associations

Cancer (therapeutic context for psoralen use in PUVA therapy)
05

Safety considerations

Off-target genotoxicityRisk of mutagenesis and secondary malignancies with therapeutic use
06

Interacting drugs

Psoralen

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