Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis
AU - Bienko, Marzena
AU - Green, Catherine M
AU - Crosetto, Nicola
AU - Rudolf, Fabian
AU - Zapart, Grzegorz
AU - Coull, Barry
AU - Kannouche, Patricia
AU - Wider, Gerhard
AU - Peter, Matthias
AU - Lehmann, Alan R
AU - Hofmann, Kay
AU - Dikic, Ivan
PY - 2005/12/16
Y1 - 2005/12/16
N2 - Translesion synthesis (TLS) is the major pathway by which mammalian cells replicate across DNA lesions. Upon DNA damage, ubiquitination of proliferating cell nuclear antigen (PCNA) induces bypass of the lesion by directing the replication machinery into the TLS pathway. Yet, how this modification is recognized and interpreted in the cell remains unclear. Here we describe the identification of two ubiquitin (Ub)-binding domains (UBM and UBZ), which are evolutionarily conserved in all Y-family TLS polymerases (pols). These domains are required for binding of poleta and poliota to ubiquitin, their accumulation in replication factories, and their interaction with monoubiquitinated PCNA. Moreover, the UBZ domain of poleta is essential to efficiently restore a normal response to ultraviolet irradiation in xeroderma pigmentosum variant (XP-V) fibroblasts. Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS.
AB - Translesion synthesis (TLS) is the major pathway by which mammalian cells replicate across DNA lesions. Upon DNA damage, ubiquitination of proliferating cell nuclear antigen (PCNA) induces bypass of the lesion by directing the replication machinery into the TLS pathway. Yet, how this modification is recognized and interpreted in the cell remains unclear. Here we describe the identification of two ubiquitin (Ub)-binding domains (UBM and UBZ), which are evolutionarily conserved in all Y-family TLS polymerases (pols). These domains are required for binding of poleta and poliota to ubiquitin, their accumulation in replication factories, and their interaction with monoubiquitinated PCNA. Moreover, the UBZ domain of poleta is essential to efficiently restore a normal response to ultraviolet irradiation in xeroderma pigmentosum variant (XP-V) fibroblasts. Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS.
KW - Amino Acid Motifs
KW - Amino Acid Sequence
KW - Animals
KW - Cell Line
KW - Computational Biology
KW - DNA/biosynthesis
KW - DNA Damage
KW - DNA Repair
KW - DNA Replication
KW - DNA-Directed DNA Polymerase/chemistry
KW - Humans
KW - Hydrophobic and Hydrophilic Interactions
KW - Models, Molecular
KW - Molecular Sequence Data
KW - Mutation
KW - Nuclear Magnetic Resonance, Biomolecular
KW - Point Mutation
KW - Proliferating Cell Nuclear Antigen/metabolism
KW - Protein Binding
KW - Protein Conformation
KW - Protein Interaction Mapping
KW - Protein Structure, Tertiary
KW - Recombinant Fusion Proteins/metabolism
KW - Transfection
KW - Ubiquitin/metabolism
KW - Xeroderma Pigmentosum/genetics
KW - Zinc Fingers
U2 - 10.1126/science.1120615
DO - 10.1126/science.1120615
M3 - Journal article
C2 - 16357261
VL - 310
SP - 1821
EP - 1824
JO - Science
JF - Science
SN - 0036-8075
IS - 5755
ER -