Sumoylation of PCNA: Wrestling with recombination at stalled replication forks.
Post-replication repair encompassses error-prone and error-free processes for bypassing lesions encountered during DNA replication. In Saccharomyces cerevisiae, proteins acting in the Rad6-dependent pathway are required to channel lesions into these pathways. Until recently there was little information as to how this channelling was regulated. However, several recent papers, and in particular from the Jentsch and Ulrich groups have provided striking insights into the role of modified forms of PCNA in these events [C. Hoege, B. Pfander, G.L. Moldovan, G. Pyrowolakis, S. Jentsch, RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO, Nature 419 (2002) 135-141; P. Stelter, H.D. Ulrich, Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation, Nature 425 (2003) 188-191; B. Pfander, G.L. Moldovan, M. Sacher, C. Hoege, S. Jentsch, SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase, Nature 436 (2005) 428-433; E. Papouli, S. Chen, A.A. Davies, D. Huttner, L. Krejci, P. Sung, H.D. Ulrich, Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p, Mol. Cell. 19 (2005) 123-133]. In particular they have shown that mono-ubiquitinated PCNA directs translesion synthesis via DNA polymerases with low stringency, and that polyubiquitinated PCNA is associated with error-free avoidance of lesions. Recent data have shown that the role of small ubiquitin-like modifier (SUMO) modification of PCNA is not an event that occurs merely in the absence of ubiquitination, rather it serves to recruit Srs2 to replication forks in order to inhibit recombination. The implications of these findings for post-replication repair in S. cerevisiae and other eukaryotes are discussed.
Watts
Felicity Z
FZ
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RR, United Kingdom. f.z.watts@sussex.ac.uk
D000818:Animals; D004261:DNA Replication; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D025842:SUMO-1 Protein / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D025842:SUMO-1 Protein; D044763:Ubiquitin-Conjugating Enzymes