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
• 30ish as trimer (2)
•review pip box proteins (3)
•RFC ( loads pcna onto chromatin)(4) (5) .
•Pol delta (6)
•Rrm3 helicase (7)
•Eco1 /Ctf7 (8)
• Cdc24 (10) (11)
•Xic –degradation of xic needs PCNA binding (12)
• Cdt1 (13) (14)
• lamin C (15)
• dacapao and pogo (17)
•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)
•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
•Hdac hus and rad9 have pcna binding site (69)
• Cdc18 (70)
• claspin (71)
• screen (73)
• lim15/dms (recA homologue) (74)
•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)
•Ubiquitylated after DNA damage and during S phase (79)
• Ubiquitylated – mono with UV and low aphidicolin. Di – on high aphidicolin ( mediated via ssDNA (80)
•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 similarity to coli dnaB. Forms ring round DNA.
• co-crystal ligase (cdc9) (84)
• crystal structure with FEN (85)
•em structures (86) (87)
•X ray structure (88) of complex with fen (89)
Cellular location and expression
•Pcna exchanges very slowly in mammalian cells after photobleaching (91) (92) but different at repair and replication sites (93)
•Into the nucleus on s and out again at the end (94)
•2nd enzyme in some species eg carrot /mouse (although mouse may be pseudogene)
•9.1.1.sugested to form a similar structure to pcna ie sliding clamp (95)
•In extracts pola needed for loading pcna (96)
•DREF site (97)
•e2f site (98)
• in cancer cells PCNA levels are 5-6 x up. Isoforms and modifications unchanged (99)
14 July 09
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