PCNA
Trimeric protein with ring shaped structure; ring encloses DNA preventing dissociation. Acts as a sliding clamp for polymerases delta and epsilon, thereby improving processivity of replicative polymerases. Also involved in DNA repair (1) . Loaded onto DNA by RFC
Synonyms |
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Molecular weight |
• 30ish as trimer (2) |
Biochemical properties |
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Motifs |
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Interactions |
•review pip box proteins (3) •RFC ( loads pcna onto chromatin)(4) (5) .
Sc •Pol delta (6) •Rrm3 helicase (7) •Eco1 /Ctf7 (8) •Mcm10 (9)
Sp • Cdc24 (10) (11) •Sumo (10)
Xl •Xic –degradation of xic needs PCNA binding (12) • Cdt1 (13) (14) • lamin C (15)
Dm •Cdt2? (16) • dacapao and pogo (17)
Mammals •Cdt1 (18) •RFC (19) (20) •Pol delta (21) - 125kDa su (6) site GX4GX8GX3YFY (22) . Some suggestion also for 50ka eg (23) (24) also p12 (25) •Pol epsilon associates late s but not early (26) , associates p50 subunit (27) •p21 ( inhibits ) (28) (29) (30) (plus many more) •Cyclin E/CDK2 (31) •Cyclin D (32) •Fen1 (33) Fen (34) 2 modes of binding on and off chromatin (35) . Disruption of interaction lethal in mice (36) •CDK2 (37) •Caf (38) (39) loads caf onto chromatin (40) •Mismatch repair proteins (41) (2 hyb) • Mcl1 (antiapoptotic) (42) • DNA methyltransferase (43) • Hmut a and b (44) qxxlixxff •p15 cif (45) • Ing ( tumour suppressor) • Hdac (46) • Cdc25 (47) • Mut1 (48) • Pms/mlh1 (49) • Xpg (50) • Ku 70/80 (51) • Srs1 with sumo form (52) (53) • Translesion polymerases (54) (55) (56) (57) -involved in loading these onto DNA in the case of damage – only interact with ub forms but seems to be some distinction between mono and di (multi) ub error prone and error free respectively (58) , may also be some ub independent effects (59) . ub stimulated by p53 and p21 (60) .Rev via brct domain (61) • P300 (62) • DNA ligase 1 (63) (64) needed for dephosphorylation of ligase (65) •Wrn (66) DQwKLlrdFdVk •Gadd45 (67) •Recq5 (68) •Hdac hus and rad9 have pcna binding site (69) • Cdc18 (70) • claspin (71) •rad18 (72)
archae • screen (73)
Coprinus cinereus • lim15/dms (recA homologue) (74)
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Modifications |
Sc •Sumolyated during S phase (75) : sumoylation stops recombination in S via Srs2 recruitment (76) •Ubiquitylated during DNA damage (52) -Multiub (mms, ubc13, rad5) (75) (2) -Mono Ub by ubc9/rad18 (77) -de ub by usp1 (78)
Sp •Ubiquitylated after DNA damage and during S phase (79)
Xenopus • Ubiquitylated – mono with UV and low aphidicolin. Di – on high aphidicolin ( mediated via ssDNA (80)
Mammal •Ubiquitylated after DNA damage (81) (54) •Phosphorylation (increases on uv treatment - (82) , increases on s entry (82) • tyr 211 phosphorylation needed for stability (83) |
Structure |
•Structure similarity to coli dnaB. Forms ring round DNA.
Sc • co-crystal ligase (cdc9) (84)
Mammals • crystal structure with FEN (85) •em structures (86) (87)
Archae •X ray structure (88) of complex with fen (89) |
Cellular location and expression |
Dm (90)
Mammals •Pcna exchanges very slowly in mammalian cells after photobleaching (91) (92) but different at repair and replication sites (93)
Starfish •Into the nucleus on s and out again at the end (94)
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Other comments |
•2nd enzyme in some species eg carrot /mouse (although mouse may be pseudogene)
Sp •9.1.1.sugested to form a similar structure to pcna ie sliding clamp (95)
Xl •In extracts pola needed for loading pcna (96)
Dm •DREF site (97)
Mammals •e2f site (98) • in cancer cells PCNA levels are 5-6 x up. Isoforms and modifications unchanged (99)
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Revised by |
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Last edited |
14 July 09 |
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