Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p.
Posttranslational modification of proliferating cell nuclear antigen (PCNA), an essential processivity clamp for DNA polymerases, by ubiquitin and SUMO contributes to the coordination of DNA replication, damage tolerance, and mutagenesis. Whereas ubiquitination in response to DNA damage promotes the bypass of replication-blocking lesions, sumoylation during S phase is damage independent. As both modifiers target the same site on PCNA, an antagonistic action of SUMO on ubiquitin-dependent DNA damage tolerance has been proposed. We now present evidence that the apparent negative effect of SUMO on lesion bypass is not due to competition with ubiquitination but is rather mediated by the helicase Srs2p, which affects genome stability by suppressing unscheduled homologous recombination. We show that Srs2p physically interacts with sumoylated PCNA, which contributes to the recruitment of the helicase to replication forks. Our findings suggest a mechanism by which SUMO and ubiquitin cooperatively control the choice of pathway for the processing of DNA lesions during replication.
Cancer Research UK, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, United Kingdom.
Efterpi
E
Papouli
Shuhua
S
Chen
Adelina A
AA
Davies
Diana
D
Huttner
Lumir
L
Krejci
Patrick
P
Sung
Helle D
HD
Ulrich
D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D018809:Proliferating Cell Nuclear Antigen; D011993:Recombinant Fusion Proteins; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; C061376:SRS2 protein, S cerevisiae; D005982:Glutathione Transferase; D004265:DNA Helicases