HPF1-dependent PARP activation promotes LIG3-XRCC1-mediated backup pathway of Okazaki fragment ligation
| Autor: | Chieko Konishi, Soichiro Kumamoto, Yoshiaki Azuma, Atsuya Nishiyama, Ryota Miyashita, Yoshie Chiba, Makoto Nakanishi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
AcademicSubjects/SCI00010
Poly (ADP-Ribose) Polymerase-1 LIG3 Xenopus Proteins Biology LIG1 DNA Ligase ATP Xenopus laevis 03 medical and health sciences Histone H3 0302 clinical medicine PARP1 Genetics Animals 030304 developmental biology chemistry.chemical_classification 0303 health sciences DNA ligase Cell-Free System Okazaki fragments Gene regulation Chromatin and Epigenetics DNA replication DNA Cell biology Chromatin X-ray Repair Cross Complementing Protein 1 chemistry 030220 oncology & carcinogenesis Ligation |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | DNA Ligase 1 (LIG1) is known as the major DNA ligase responsible for Okazaki fragment joining. Recent studies have implicated LIG3 complexed with XRCC1 as an alternative player in Okazaki fragment joining in cases where LIG1 is not functional, although the underlying mechanisms are largely unknown. Here, using a cell-free system derived fromXenopusegg extracts, we demonstrated the essential role of PARP1-HPF1 in LIG3-dependent Okazaki fragment joining. We found that Okazaki fragments were eventually ligated even in the absence of LIG1, employing in its place LIG3-XRCC1 which was recruited onto chromatins. Concomitantly, LIG1 deficiency induces ADP-ribosylation of histone H3 in a PARP1-HPF1-dependent manner. The depletion of PARP1 or HPF1 resulted in a failure to recruit LIG3 onto chromatin and a subsequent failure in Okazaki fragment joining in LIG1-depleted extracts. Importantly, Okazaki fragments were not ligated at all when LIG1 and XRCC1 were co-depleted. Our results suggest that a unique form of ADP-ribosylation signalling promotes the recruitment of LIG3 on chromatins and its mediation of Okazaki fragment joining as a backup system for LIG1 perturbation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|