Experimental studies showed that high energy radiation induced base release and DNA backbone breaks mainly occur at the neighboring 5' nucleotide when a single-stranded DNA is modified by radiosensitizing 5-halogenated deoxyuridines. However, no mechanism can be used to interpret these experimental observations. To better understand the radiosensitivity of 5-halogenated deoxyuridines, mechanisms involving hydrogen abstraction by the uracil-5-yl radical from the C2' and C3' positions of an adjacent nucleotide separately followed by the C3'-O3' or N-glycosidic bond rupture and the P-O3' bond breakage are investigated in the DNA sequence 5'-TU(•)-3' employing density functional theory calculations in the present study. It is found that hydrogen abstractions from both positions are comparable with the one from the C2' site slightly more favorable. The N-glycosidic bond cleavage in the neighboring 5' nucleotide following the internucleotide C2'-Ha abstraction is estimated to have the lowest activation free energies, indicating that the adjacent 5' base release dominates electron induced damage to single-stranded DNA incorporated by 5-halogenated deoxyuridines. Relative to the P-O3' bond breakage after the internucleotide C3'-H abstraction, the C3'-O3' bond rupture in the neighboring 5' nucleotide following the internucleotide C2'-Ha abstraction is predicted to have a lower activation free energy, implying that single-stranded DNA backbone breaks are prone to occur at the C3'-O3' bond site. The 5'-TU(•)-3' species has substantial electron affinity and can even capture a hydrated electron, forming the 5'-TU(-)-3' anion. However, the electron induced C3'-O3' bond rupture in 5'-TU(-)-3' anion via a pathway of internucleotide proton abstraction is only minor in both the gas phase and aqueous solution. The present theoretical predictions can interpret rationally experimental observations, thereby demonstrating that the mechanisms proposed here are responsible for high energy radiation induced damage to single-stranded DNA incorporated by radiosensitizing 5-halogenated deoxyuridines. By comparing with previous results, our work proves that the radiosensitizing action of 5-bromo-2-deoxyuridine is not weaker but stronger than its isomer 6-bromo-2-deoxyuridine on the basis of the available data.