TY - JOUR
T1 - Proliferating cell nuclear antigen-dependent coordination of the biological functions of human DNA polymerase
AU - Vidal, Antonio E.
AU - Kannouche, Patricia
AU - Podust, Vladimir N.
AU - Yang, Wei
AU - Lehmann, Alan R.
AU - Woodgate, Roger
PY - 2004/11/12
Y1 - 2004/11/12
N2 - Y-family DNA polymerases are believed to facilitate the replicative bypass of damaged DNA in a process commonly referred to as translesion synthesis. With the exception of DNA polymerase η (polη), which is defective in humans with the Xeroderma pigmentosum variant (XP-V) phenotype, little is known about the cellular function(s) of the remaining human Y-family DNA polymerases. We report here that an interaction between human DNA polymerase ι (polι) and the proliferating cell nuclear antigen (PCNA) stimulates the processivity of polι in a template-dependent manner in vitro. Mutations in one of the putative PCNA-binding motifs (PIP box) of polι or the interdomain connector loop of PCNA diminish the binding between polι and PCNA and concomitantly reduce PCNA-dependent stimulation of poli activity. Furthermore, although retaining its capacity to interact with polη in vivo, the polι-PIP box mutant fails to accumulate in replication foci. Thus, PCNA, acting as both a scaffold and a modulator of the different activities involved in replication, appears to recruit and coordinate replicative and translesion DNA synthesis polymerases to ensure genome integrity.
AB - Y-family DNA polymerases are believed to facilitate the replicative bypass of damaged DNA in a process commonly referred to as translesion synthesis. With the exception of DNA polymerase η (polη), which is defective in humans with the Xeroderma pigmentosum variant (XP-V) phenotype, little is known about the cellular function(s) of the remaining human Y-family DNA polymerases. We report here that an interaction between human DNA polymerase ι (polι) and the proliferating cell nuclear antigen (PCNA) stimulates the processivity of polι in a template-dependent manner in vitro. Mutations in one of the putative PCNA-binding motifs (PIP box) of polι or the interdomain connector loop of PCNA diminish the binding between polι and PCNA and concomitantly reduce PCNA-dependent stimulation of poli activity. Furthermore, although retaining its capacity to interact with polη in vivo, the polι-PIP box mutant fails to accumulate in replication foci. Thus, PCNA, acting as both a scaffold and a modulator of the different activities involved in replication, appears to recruit and coordinate replicative and translesion DNA synthesis polymerases to ensure genome integrity.
UR - http://www.scopus.com/inward/record.url?scp=9144258471&partnerID=8YFLogxK
U2 - 10.1074/jbc.M406511200
DO - 10.1074/jbc.M406511200
M3 - Article
C2 - 15342632
AN - SCOPUS:9144258471
SN - 0021-9258
VL - 279
SP - 48360
EP - 48368
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -