Open AccessCRL4Cdt2 ubiquitin ligase regulates Dna2 and Rad16 (XPF) nucleases by targeting Pxd1 for degradation
Author(s) -
Jiamin Zhang,
Jinxin Zheng,
Yue-He Ding,
Xiaoran Zhang,
Fang Suo,
Jingyi Ren,
MengQiu Dong,
Li-Lin Du
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1008933
Subject(s) - biology , degron , ubiquitin ligase , schizosaccharomyces , schizosaccharomyces pombe , ubiquitin , dna ligase , microbiology and biotechnology , nuclease , dna repair , ubiquitin protein ligases , dna , biochemistry , yeast , saccharomyces cerevisiae , gene
Structure-specific endonucleases (SSEs) play key roles in DNA replication, recombination, and repair. SSEs must be tightly regulated to ensure genome stability but their regulatory mechanisms remain incompletely understood. Here, we show that in the fission yeast Schizosaccharomyces pombe , the activities of two SSEs, Dna2 and Rad16 (ortholog of human XPF), are temporally controlled during the cell cycle by the CRL4 Cdt2 ubiquitin ligase. CRL4 Cdt2 targets Pxd1, an inhibitor of Dna2 and an activator of Rad16, for degradation in S phase. The ubiquitination and degradation of Pxd1 is dependent on CRL4 Cdt2 , PCNA, and a PCNA-binding degron motif on Pxd1. CRL4 Cdt2 -mediated Pxd1 degradation prevents Pxd1 from interfering with the normal S-phase functions of Dna2. Moreover, Pxd1 degradation leads to a reduction of Rad16 nuclease activity in S phase, and restrains Rad16-mediated single-strand annealing, a hazardous pathway of repairing double-strand breaks. These results demonstrate a new role of the CRL4 Cdt2 ubiquitin ligase in genome stability maintenance and shed new light on how SSE activities are regulated during the cell cycle.