The chromatin remodeler ERCC6 and the histone chaperone NAP1 are involved in apurinic/apyrimidinic endonuclease-mediated DNA repair

Abstract

During base excision repair (BER), the apurinic or apyrimidinic (AP) site serves as an intermediate product following base excision. In plants, APE-redox protein (ARP) represents the major AP site of cleavage activity. Despite the well-established understanding that the nucleosomal structure acts as a barrier to various DNA-templated processes, the regulatory mechanisms underlying BER at the chromatin level remain elusive, especially in plants. In this study, we identified plant chromatin remodeler Excision Repair Cross-Complementing protein group 6 (ERCC6) and histone chaperone Nucleosome Assembly Protein 1 (NAP1) as interacting proteins with ARP. The catalytic ATPase domain of ERCC6 facilitates its interaction with both ARP and NAP1. Additionally, ERCC6 and NAP1 synergistically contribute to nucleosome sliding and exposure of hindered endonuclease cleavage sites. Loss-of-function mutations in Arabidopsis (Arabidopsis thaliana) ERCC6 or NAP1 resulted in arp-dependent plant hypersensitivity to 5-fluorouracil (5-FU), a toxic agent inducing BER, and the accumulation of AP sites. Furthermore, similar protein interactions are also found in yeast cells, suggesting a conserved recruitment mechanism employed by the AP endonuclease to overcome chromatin barriers during BER progression.

RFC1regulates the expansion of neural progenitors in the developing zebrafish cerebellum

“…We also found increased expression of multiple genes involved in DNA repair processes, such as cenpx, xpc, ercc5/6 and rpa1/2 Figure 5A, 5B). Those DNA repair and tumour-suppressor genes are activated by cell cycle checkpoint controllers upon alteration in DNA integrity [49][50][51][52][53] . Finally, we showed that the expression of multiple pro-apoptotic genes (tp53, baxa, casp8, mdm2, mdm4) [54][55][56][57] and p53 target genes (rrm2, ccng1, rps37l sesn1, sesn3) is increased in these same clusters (Figure 5A, 5B).…”