TY - JOUR
T1 - The HARP-like Domain-Containing Protein AH2/ZRANB3 Binds to PCNA and Participates in Cellular Response to Replication Stress
AU - Yuan, Jingsong
AU - Ghosal, Gargi
AU - Chen, Junjie
N1 - Funding Information:
We thank all members of the Chen laboratory for their advice and technical assistance, especially Wenqi Wang. We thank Henry Adams and the Genetics Department Microscopy CORE facility at MD Anderson Cancer Center. This work was supported in part by grants from the National Institutes of Health to J.C. (CA089239, CA092312, and CA100109). J.C. is also a recipient of an Era of Hope Scholar award from the Department of Defense (W81XWH-05-1-0470) and is a member of the MD Anderson Cancer Center (CA016672).
PY - 2012/8/10
Y1 - 2012/8/10
N2 - Proteins with annealing activity are newly identified ATP-dependent motors that can rewind RPA-coated complementary single-stranded DNA bubbles. AH2 (annealing helicase 2, also named as ZRANB3) is the second protein with annealing activity, the function of which is still unknown. Here, we report that AH2 is recruited to stalled replication forks and that cells depleted of AH2 are hypersensitive to replication stresses. Furthermore, AH2 binds to PCNA, which is crucial for its function at stalled replication forks. Interestingly, we identified a HARP-like (HPL) domain in AH2 that is indispensible for its annealing activity in vitro and its function in vivo. Moreover, searching of HPL domain in SNF2 family of proteins led to the identification of SMARCA1 and RAD54L, both of which possess annealing activity. Thus, this study not only demonstrates the in vivo functions of AH2, but also reveals a common feature of this new subfamily of proteins with annealing activity.
AB - Proteins with annealing activity are newly identified ATP-dependent motors that can rewind RPA-coated complementary single-stranded DNA bubbles. AH2 (annealing helicase 2, also named as ZRANB3) is the second protein with annealing activity, the function of which is still unknown. Here, we report that AH2 is recruited to stalled replication forks and that cells depleted of AH2 are hypersensitive to replication stresses. Furthermore, AH2 binds to PCNA, which is crucial for its function at stalled replication forks. Interestingly, we identified a HARP-like (HPL) domain in AH2 that is indispensible for its annealing activity in vitro and its function in vivo. Moreover, searching of HPL domain in SNF2 family of proteins led to the identification of SMARCA1 and RAD54L, both of which possess annealing activity. Thus, this study not only demonstrates the in vivo functions of AH2, but also reveals a common feature of this new subfamily of proteins with annealing activity.
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U2 - 10.1016/j.molcel.2012.05.025
DO - 10.1016/j.molcel.2012.05.025
M3 - Article
C2 - 22705370
AN - SCOPUS:84864923437
SN - 1097-2765
VL - 47
SP - 410
EP - 421
JO - Molecular cell
JF - Molecular cell
IS - 3
ER -