PrimPol-mediated repriming facilitates replication traverse of DNA interstrand crosslinks

ABSTRACT: DNA interstrand crosslinks (ICLs) induced by endogenous aldehydes or chemotherapeutic agents interfere with essential processes such as replication and transcription. ICL recognition and repair by the Fanconi Anemia pathway requires the formation of an X-shaped DNA structure that may arise from convergence of two replication forks at the crosslink, or traversing of the lesion by a single replication fork. Here, we report that ICL traverse strictly requires DNA repriming events downstream of the lesion, which are carried out by PrimPol, the second primase-polymerase identified in mammalian cells after Pol?/Primase. The recruitment of PrimPol to the vicinity of ICLs depends on its interaction with RPA, but not on FANCM translocase or the BLM/TOP3A/RMI1-2 (BTR) complex that also participate i

SUBMITTER: Dr. Daniel Gonzalez-Acosta 

PROVIDER: S-SCDT-EMBOJ-2020-106355 | biostudies-other |

REPOSITORIES: biostudies-other