| Autor: |
Rua-Fernandez J, Lovejoy CA, Mehta KPM, Paulin KA, Toudji YT, Eichman BF, Cortez D |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Jun 14. Date of Electronic Publication: 2023 Jun 14. |
| DOI: |
10.1101/2023.06.14.544844 |
| Abstrakt: |
Abasic sites are common DNA lesions that stall polymerases and threaten genome stability. When located in single-stranded DNA (ssDNA), they are shielded from aberrant processing by HMCES via a DNA-protein crosslink (DPC) that prevents double-strand breaks. Nevertheless, the HMCES-DPC must be removed to complete DNA repair. Here, we found that DNA polymerase α inhibition generates ssDNA abasic sites and HMCES-DPCs. These DPCs are resolved with a half-life of approximately 1.5 hours. Resolution does not require the proteasome or SPRTN protease. Instead, HMCES-DPC self-reversal is important for resolution. Biochemically, self-reversal is favored when the ssDNA is converted to duplex DNA. When the self-reversal mechanism is inactivated, HMCES-DPC removal is delayed, cell proliferation is slowed, and cells become hypersensitive to DNA damage agents that increase AP site formation. Thus, HMCES-DPC formation followed by self-reversal is an important mechanism for ssDNA AP site management. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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